This invention relates to novel lactams having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Axcex2-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to xcex2-amyloid production such as Alzheimer""s disease and Down""s Syndrome.
Alzheimer""s disease (AD) is a degenerative brain disorder characterized clinically by progressive loss of memory, temporal and local orientation, cognition, reasoning, judgment and emotionally stability. AD is a common cause of progressive dementia in humans and is one of the major causes of death in the United States. AD has been observed in all races and ethnic groups worldwide, and is a major present and future health problem. No treatment that effectively prevents AD or reverses the clinical symptoms and underlying pathophysiology is currently available (for review, Dennis J. Selkoe; Cell Biology of the amyloid (beta)-protein precursor and the mechanism of Alzheimer""s disease, Annu Rev Cell Biol, 1994, 10: 373-403).
Histopathological examination of brain tissue derived upon autopsy or from neurosurgical specimens in effected individuals revealed the occurrence of amyloid plaques and neurofibrillar tangles in the cerebral cortex of such patients. Similar alterations were observed in patients with Trisomy 21 (Down""s syndrome), and hereditary cerebral hemorrhage with amyloidosis of the Dutch-type.
Neurofibrillar tangles are nonmembrane-bound bundles of abnormal proteinaceous filaments and biochemical and immunochemical studies led to the conclusion that their principle protein subunit is an altered phosphorylated form of the tau protein (reviewed in Selkoe, 1994).
Biochemical and immunological studies revealed that the dominant proteinaceous component of the amyloid plaque is an approximately 4.2 kilodalton (kD) protein of about 39 to 43 amino acids. This protein was designated Axcex2, xcex2-amyloid peptide, and sometimes xcex2/A4; referred to herein as Axcex2. In addition to its deposition in amyloid plaques, Axcex2 is also found in the walls of meningeal and parenchymal arterioles, small arteries, capillaries, and sometimes, venules. Axcex2 was first purified and a partial amino acid reported in 1984 (Glenner and Wong, Biochem. Biophys. Res. Commun. 120: 885-890). The isolation and sequence data for the first 28 amino acids are described in U.S. Pat. No. 4,666,829.
Compelling evidence accumulated during the last decade revealed that Axcex2 is an internal polypeptide derived from a type 1 integral membrane protein, termed xcex2 amyloid precursor protein (APP). xcex2 APP is normally produced by many cells both in vivo and in cultured cells, derived from various animals and humans. Axcex2 is derived from cleavage of xcex2 APP by as yet unknown enzyme (protease) system(s), collectively termed secretases.
The existence of at least four proteolytic activities has been postulated. They include xcex2 secretase(s), generating the N-terminus of Axcex2, a secretase(s) cleaving round the 16/17 peptide bond in Axcex2, and xcex3 secretases, enerating C-terminal Axcex2 fragments ending at position 38, 39, 40, 42, and 43 or generating C-terminal extended precursors which are subsequently truncated to the above polypeptides.
Several lines of evidence suggest that abnormal accumulation of Axcex2 plays a key role in the pathogenesis of AD. Firstly, Axcex2 is the major protein found in amyloid plaques. Secondly, Axcex2 is neurotoxic and may be causally related to neuronal death observed in AD patients. Thirdly, missense DNA mutations at position 717 in the 770 isoform of xcex2 APP can be found in effected members but not unaffected members of several families with a genetically determined (familiar) form of AD. In addition, several other xcex2 APP mutations have been described in familiar forms of AD. Fourthly, similar neuropathological changes have been observed in transgenic animals overexpressing mutant forms of human xcex2 APP. Fifthly, individuals with Down""s syndrome have an increased gene dosage of xcex2 APP and develop Eearly-onset AD. Taken together, these observations strongly suggest that Axcex2 depositions may be causally related to the AD.
It is hypothesized that inhibiting the production of Axcex2 will prevent and reduce neurological degeneration, by controlling the formation of amyloid plaques, reducing neurotoxicity and, generally, mediating the pathology associated with Axcex2 production. One method of treatment methods would therefore be based on drugs that inhibit the formation of Axcex2 in vivo.
Methods of treatment could target the formation of Axcex2 through the enzymes involved in the proteolytic processing of xcex2 amyloid precursor protein. Compounds that inhibit xcex2 or xcex3 secretase activity, either directly or indirectly, could control the production of Axcex2. Advantageously, compounds that specifically target xcex3 secretases, could control the production of Axcex2. Such inhibition of xcex2 or xcex3secretases could thereby reduce production of Axcex2, which, thereby, could reduce or prevent the neurological disorders associated with Axcex2 protein.
One object of the present invention is to provide novel compounds which are useful as inhibitors of the production of Axcex2 protein or pharmaceutically acceptable salts or prodrugs thereof.
It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt form or prodrug form thereof.
It is another object of the present invention to provide a method for treating degenerative neurological disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt form or prodrug form thereof.
These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors"" discovery that compounds of Formula (I): 
or pharmaceutically acceptable salt form or prodrug forms thereof, wherein Q, R2, R3, R5, R5a, R6, B, W, X, Y, and Z are defined below, are effective inhibitors of the production of Axcex2.
Thus, in a first embodiment, the present invention provides a novel compound of Formula (I): 
or a pharmaceutically acceptable salt form or prodrug thereof, wherein:
Q is Q1,
(C1-C3 alkyl)-Oxe2x80x94Q1,
(C1-C3 alkyl)-Sxe2x80x94Q1,
(C1-C3 alkyl)-S(xe2x95x90O)xe2x80x94Q1,
(C1-C3 alkyl)-S(xe2x95x90O)2xe2x80x94Q1, or
(C1-C3 alkyl)-N(R20)xe2x80x94Q1;
Q1 is C1-C8 alkyl substituted with 0-3 R1a;
C2-C8 alkenyl substituted with 0-3 R1a;
C2-C8 alkynyl substituted with 0-3 R1a;
C3-C10 cycloalkyl substituted with 0-3 R1b;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, and (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94;
R2 is H, methyl, ethyl, propyl, or butyl;
R3 is H, C1-C6 alkyl, xe2x80x94C(xe2x95x90O)(C1-C6 alkyl), xe2x80x94C(xe2x95x90S)(C1-C6 alkyl), or xe2x80x94C(xe2x95x90O)NR21R22;
alternatively, R2 and OR3 are combined to form Cxe2x95x90O or Cxe2x95x90Nxe2x80x94OH;
R5 is H, OR14;
C1-C6 alkyl substituted with 0-3 R5b;
C1-C6 alkoxy substituted with 0-3 R5b;
C2-C6 alkenyl substituted with 0-3 R5b;
C2-C6 alkynyl substituted with 0-3 R5b;
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3R5c;
R5a is H, C1-C4 alkyl, or C2-C4 alkenyl;
alternatively, R5 and R5a may be combined to form a 3-7 membered cycloalkyl ring substituted with 0-3 R5c; optionally the cycloalkyl ring formed by combining R5 and R5a may be benzo fused, wherein the benzo fused ring may be substituted with 0-3 R5c;
R5b, at each occurrence, is independently selected from:
H, C1-C6 alkyl, CF3, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C2-C6 alkenyl, C2-C6 alkynyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94,
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R5c;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R6 is H or C1-C6 alkyl;
W is (CR8R8a)pxe2x80x94;
p is 0, 1, 2, 3, or 4;
R8 and R8a, at each occurrence, are independently selected from H, F, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl and C3-C8 cycloalkyl;
X is a bond;
C6-C10 aryl substituted with 0-3 RXb;
C3-C10 cycloalkyl substituted with 0-3 RXb;
C3-C10 carbocycle substituted with 0-3 RXb; or
5 to 10 membered heterocycle substituted with 0-2 RXb;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
Y is a bond or (CR9R9a)txe2x80x94Vxe2x80x94(CR9R9a)uxe2x80x94;
t is 0, 1, 2, or 3;
u is 0, 1, 2, or 3;
R9 and R9a, at each occurrence, are independently selected from H, F, C1-C6 alkyl or C3-C8 cycloalkyl;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94N(R19)xe2x80x94, xe2x80x94C(xe2x95x90O)NR19bxe2x80x94, xe2x80x94NR19bC(xe2x95x90O)xe2x80x94, xe2x80x94NR19bS(xe2x95x90O)2xe2x80x94, xe2x80x94S(xe2x95x90O)2NR19bxe2x80x94, xe2x80x94C(xe2x95x90O)Oxe2x80x94, or xe2x80x94OC(xe2x95x90O)xe2x80x94;
Z is H;
C1-C8 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
Ring B is a 6, 7, or 8 membered lactam,
wherein the lactam is saturated, partially saturated or unsaturated;
wherein each additional lactam carbon is substituted with 0-2 R11; and,
optionally, the lactam contains a heteroatom selected from xe2x80x94Nxe2x95x90, xe2x80x94NHxe2x80x94, xe2x80x94N(R10)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, and xe2x80x94S(xe2x95x90O)2xe2x80x94;
additionally, two R11 substituents on adjacent atoms may be combined to form C3-C6 carbocycle fused radical, a benzo fused radical, or a 5 to 6 membered heteroaryl fused radical,
wherein said 5 to 6 membered heteroaryl fused radical comprises 1-2 heteroatoms selected from N, O, and S;
wherein said benzo fused radical or 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R13;
R10 is H, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, S(xe2x95x90O)2R17;
C1-C6 alkyl substituted with 0-2 R10a;
C6-C10 aryl substituted with 0-4 R10b;
C3-C10 carbocycle substituted with 0-3 R10b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is optionally substituted with 0-3 R10b;
R10a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3;
aryl substituted with 0-4 R10b;
C3-C10 carbocycle substituted with 0-3 R10b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is optionally substituted with 0-3 R10b;
R10b, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R11, at each occurrence, is independently selected from H, C1-C4 alkoxy, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR18R19, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, CF3;
C1-C6 alkyl substituted with 0-1 R11a;
C6-C10 aryl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
R11a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, C1-C6 alkyl, and C2-C6 alkoxyalkyl;
R14a is H, phenyl, benzyl, or C1-C6 alkyl;
R15, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R16, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR15R16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R17 is H, C1-C6 alkyl, or C2-C6 alkoxyalkyl,
aryl substituted by 0-4 R17a, or
aryl-CH2xe2x80x94 wherein said aryl is substituted by by 0-4 R17a;
R17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, xe2x80x94OH, F, Cl, Br, I, CF3, OCF3, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, xe2x80x94NH2, xe2x80x94N(CH3)2, or C1-C4 haloalkyl;
R18, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR17R18 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R19, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R19b, at each occurrence, is independently selected from H and C1-C6 alkyl;
R20 is H, OH, C1-C4 alkyl, phenyl, benzyl, or phenethyl;
R21 at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, and phenethyl; and
R22, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, and phenethyl.
[1] In another embodiment the present invention provides a compound of Formula (I): 
or a pharmaceutically acceptable salt form or prodrug thereof, wherein:
Q is Q1,
(C1-C3 alkyl)-Oxe2x80x94Q1,
(C1-C3 alkyl)-Sxe2x80x94Q1,
(C1-C3 alkyl)-S (xe2x95x90O)xe2x80x94Q1,
(C1-C3 alkyl)-S(xe2x95x90O)2xe2x80x94Q1, or
(C1-C3 alkyl)-N(R20)xe2x80x94Q1;
Q1 is C1-C8 alkyl substituted with 0-3 R1a;
C2-C8 alkenyl substituted with 0-3 R1a;
C2-C8 alkynyl substituted with 0-3 R1a;
C3-C10 cycloalkyl substituted with 0-3 R1b;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, and (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94;
R2 is H, methyl, ethyl, propyl, or butyl;
R3 is H, C1-C6 alkyl, xe2x80x94C(xe2x95x90O)(C1-C6 alkyl), xe2x80x94C(xe2x95x90S)(C1-C6 alkyl), or xe2x80x94C(xe2x95x90O)NR21R22;
alternatively, R2 and OR3 are combined to form Cxe2x95x90O or Cxe2x95x90Nxe2x80x94OH;
R5 is H, OR14;
C1-C6 alkyl substituted with 0-3 R5b;
C1-C6 alkoxy substituted with 0-3 R5b;
C2-C6 alkenyl substituted with 0-3 R5b;
C2-C6 alkynyl substituted with 0-3 R5b;
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3R5c;
R5a is H, C1-C4 alkyl, or C2-C4 alkenyl;
alternatively, R5 and R5a may be combined to form a 3-7 membered cycloalkyl ring substituted with 0-3 R5c; optionally the cycloalkyl ring formed by combining R5 and R5a may be benzo fused, wherein the benzo fused ring may be substituted with 0-3 R5c;
R5b, at each occurrence, is independently selected from:
H, C1-C6 alkyl, CF3, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C2-C6 alkenyl, C2-C6 alkynyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94,
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R5c;
R5c, at each occurrence, is independently selected from H, OH, C1, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R6 is H or C1-C6 alkyl;
W is xe2x80x94(CR8R8a)pxe2x80x94;
p is 0, 1, 2, 3, or 4;
R8 and R8a, at each occurrence, are independently selected from H, F, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl and C3-C8 cycloalkyl;
X is a bond;
C6-C10 aryl substituted with 0-3 RXb;
C3-C10 cycloalkyl substituted with 0-3 RXb;
C3-C10 carbocycle substituted with 0-3 RXb; or
5 to 10 membered heterocycle substituted with 0-2 RXb;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
Y is a bond or xe2x80x94(CR9R9a)txe2x80x94Vxe2x80x94(CR9R9a)uxe2x80x94;
t is 0, 1, 2, or 3;
u is 0, 1, 2, or 3;
R9 and R9a, at each occurrence, are independently selected from H, F, C1-C6 alkyl or C3-C8 cycloalkyl;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94N(R19)xe2x80x94, xe2x80x94C(xe2x95x90O)NR19bxe2x80x94, xe2x80x94NR19bC(xe2x95x90O)xe2x80x94, xe2x80x94NR19bS(xe2x95x90O)2xe2x80x94, xe2x80x94S(xe2x95x90O)2NR19bxe2x80x94, xe2x80x94C(xe2x95x90O)Oxe2x80x94, or xe2x80x94OC(xe2x95x90O)xe2x80x94;
Z is H;
C1-C8 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
Ring B is a 6, 7, or 8 membered lactam,
wherein the lactam is saturated, partially saturated or unsaturated;
wherein each additional lactam carbon is substituted with 0-2 R11; and,
optionally, the lactam contains a heteroatom selected from xe2x80x94Nxe2x95x90, xe2x80x94N+(xe2x80x94Oxe2x88x92)xe2x95x90, xe2x80x94NHxe2x80x94, xe2x80x94N(R10)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, and xe2x80x94S(xe2x95x90O)2xe2x80x94;
additionally, two R11 substituents on adjacent atoms may be combined to form C3-C6 carbocycle fused radical, a benzo fused radical, or a 5 to 6 membered heteroaryl fused radical,
wherein said 5 to 6 membered heteroaryl fused radical comprises 1-2 heteroatoms selected from N, O, and S;
wherein said benzo fused radical or 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R13;
R10 is H, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, S(xe2x95x90O)2R17;
C1-C6 alkyl substituted with 0-2 R10a;
C6-C10 aryl substituted with 0-4 R10b;
C3-C10 carbocycle substituted with 0-3 R10b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is optionally substituted with 0-3 R10b;
R10a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3;
aryl substituted with 0-4 R10b;
C3-C10 carbocycle substituted with 0-3 R10b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is optionally substituted with 0-3 R10b;
R10b, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R11, at each occurrence, is independently selected from H, C1-C4 alkoxy, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR18R19, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, CF3;
C1-C6 alkyl substituted with 0-1 R11a;
C6-C10 aryl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
R11a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR4, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, benzyl, benzoyl, C(xe2x95x90O)CH3, t-butoxycarbonyl, and 3,5-dimethyl-isoxazole-S(xe2x95x90O)2xe2x80x94;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R161 and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, C1-C6 alkyl, and C2-C6 alkoxyalkyl;
R14a is H, phenyl, benzyl, or C1-C6 alkyl;
R15, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R16, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR15R16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R17 is H, C1-C6 alkyl, or C2-C6 alkoxyalkyl,
aryl substituted by 0-4 R17a, or
aryl-CH2xe2x80x94 wherein said aryl is substituted by by 0-4 R17a;
R17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, xe2x80x94OH, F, Cl, Br, I, CF3, OCF3, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, xe2x80x94NH2, xe2x80x94N(CH3)2, or C1-C4 haloalkyl;
R18, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR18R19 may be a heterocyclic ring selected from the group: piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; wherein said heterocyclic ring is substituted with 0-3 R11bxe2x80x94;
R19, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R19b, at each occurrence, is independently selected from H and C1-C6 alkyl;
R20 is H, OH, C1-C4 alkyl, phenyl, benzyl, or phenethyl;
R21, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, and phenethyl; and
R22, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, and phenethyl.
[2] In a preferred embodiment the present invention provides a compound of Formula (I) wherein:
Q is Q1,
(C1-C3 alkyl)-Oxe2x80x94Q1,
(C1-C3 alkyl)-Sxe2x80x94Q1,
(C1-C3 alkyl)-S(xe2x95x90O)xe2x80x94Q1,
(C1-C3 alkyl)-S(xe2x95x90O)2xe2x80x94Q1, or
(C1-C3 alkyl)-N(R20)xe2x80x94Q1;
Q1 is C1-C6 alkyl substituted with 0-3 R1a;
C2-C6 alkenyl substituted with 0-3 R1a;
C2-C6 alkynyl substituted with 0-3 R1a;
C3-C10 cycloalkyl substituted with 0-3 R1b;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, and (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94;
R2 is H, methyl, ethyl, propyl, or butyl;
R3 is H, C1-C4 alkyl, xe2x80x94C(xe2x95x90O)(C1-C4 alkyl), xe2x80x94C(xe2x95x90S)(C1-C4 alkyl), or xe2x80x94C(xe2x95x90O)NR21R22;
R5 is H, OR14;
C1-C6 alkyl substituted with 0-3 R5b;
C1-C6 alkoxy substituted with 0-3 R5b;
C2-C6 alkenyl substituted with 0-3 R5b;
C2-C6 alkynyl substituted with 0-3 R5b;
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3R5c;
R5a is H, C1-C4 alkyl, or C2-C4 alkenyl; alternatively, R5 and R5a may be combined to form a 3-7 membered cycloalkyl ring substituted with 0-3 R5c;
R5b, at each occurrence, is independently selected from:
H, C1-C6 alkyl, CF3, OR14, C1, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C2-C6 alkenyl, C2-C6 alkynyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94,
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R5c;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R6 is H, methyl, or ethyl;
W is (CR8R8a)pxe2x80x94;
p is 0, 1, or 2;
R8 and R8a, at each occurrence, are independently selected from H, F, methyl, and ethyl;
X is a bond;
phenyl substituted with 0-3 RXb;
C3-C6 cycloalkyl substituted with 0-3 RXb; or
5 to 6 membered heterocycle substituted with 0-2 RXb;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
Y is a bond or xe2x80x94(CR9R9a)txe2x80x94Vxe2x80x94(CR9R9a)uxe2x80x94;
t is 0, 1, or 2;
u is 0, 1, or 2;
R9 and R9a, at each occurrence, are independently selected from H, F, methyl, and ethyl;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94N(R19)xe2x80x94, xe2x80x94C(xe2x95x90O)NHxe2x80x94, xe2x80x94NHC(xe2x95x90O)xe2x80x94, xe2x80x94NHS(xe2x95x90O)2xe2x80x94, or xe2x80x94S(xe2x95x90O)2NHxe2x80x94;
Z is H, halo;
C1-C4 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
Ring B is a 7 membered lactam,
wherein the lactam is saturated, partially saturated or unsaturated;
wherein each additional lactam carbon is substituted with 0-2 R11; and,
optionally, the lactam contains a heteroatom selected from xe2x80x94Nxe2x95x90, xe2x80x94NHxe2x80x94, xe2x80x94N(R10)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, and xe2x80x94S(xe2x95x90O)2xe2x80x94;
additionally, two R11 substituents on adjacent atoms may be combined to form C3-C6 carbocycle fused radical, a benzo fused radical, or a 5 to 6 membered heteroaryl fused radical,
wherein said 5 to 6 membered heteroaryl fused radical comprises 1-2 heteroatoms selected from N, O, and S;
wherein said benzo fused radical or 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R13;
R10 is H, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, S(xe2x95x90O)2R17;
C1-C6 alkyl substituted with 0-2 R10a;
C6-C10 aryl substituted with 0-4 R10b;
C3-C10 carbocycle substituted with 0-3 R10b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is optionally substituted with 0-3 R10b;
R10a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3, or aryl substituted with 0-4 R10b;
R10b, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R11, at each occurrence, is independently selected from H, C1-C4 alkoxy, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR18R19, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, CF3;
C1-C6 alkyl substituted with 0-1 R11a;
C6-C10 aryl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
R11a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, C1-C6 alkyl, and C2-C6 alkoxyalkyl;
R15, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R16 at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR15R16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R17 is H, aryl, aryl-CH2xe2x80x94, C1-C6 alkyl, or C2-C6 alkoxyalkyl;
R18, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R19, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR17R18 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R20 is H, OH, C1-C4 alkyl, phenyl, benzyl, or phenethyl;
R21, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, and phenethyl; and
R22, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, and phenethyl.
[3] In a preferred embodiment the present invention provides a compound of Formula (I) wherein Ring B is selected from: 
wherein each benzo fused radical is substituted with 0-3 R13.
[4] In a preferred embodiment the present invention provides a compound of Formula (Ia): 
or a pharmaceutically acceptable salt form or prodrug thereof, wherein:
Q is Q1,
(C1-C3 alkyl)-Oxe2x80x94Q1,
(C1-C3 alkyl)-Sxe2x80x94Q1,
(C1-C3 alkyl)-S(xe2x95x90O)xe2x80x94Q1,
(C1-C3 alkyl)-S(xe2x95x90O)2xe2x80x94Q1, or
(C1-C3 alkyl)-N(R20)xe2x80x94Q1;
Q1 is C1-C6 alkyl substituted with 0-3 R1a;
C2-C6 alkenyl substituted with 0-3 R1a;
C2-C6 alkynyl substituted with 0-3 R1a;
C3-C10 cycloalkyl substituted with 0-3 R1b;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, and (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94;
R2 is H, methyl, or ethyl;
R5 is H, OR14;
C1-C6 alkyl substituted with 0-3 R5b;
C1-C6 alkoxy substituted with 0-3 R5b;
C2-C6 alkenyl substituted with 0-3 R5b;
C2-C6 alkynyl substituted with 0-3 R5b;
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3R5c;
R5a is H, C1-C4 alkyl, or C2-C4 alkenyl;
alternatively, R5 and R5a may be combined to form a 3-7 membered cycloalkyl ring substituted with 0-3 R5c;
R5b, at each occurrence, is independently selected from:
H, C1-C6 alkyl, CF3, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C2-C6 alkenyl, C2-C6 alkynyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94,
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R5c;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
W is xe2x80x94(CR8R8a)pxe2x80x94;
p is 0, 1, or 2;
R8 and R8a, at each occurrence, are independently selected from H, F, methyl, and ethyl;
X is a bond;
phenyl substituted with 0-3 RXb;
C3-C6 cycloalkyl substituted with 0-3 RXb; or
5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-2 RXb;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
Y is a bond or xe2x80x94(CR9R9a)txe2x80x94Vxe2x80x94(CR9R9a)uxe2x80x94;
t is 0, 1, or 2;
u is 0, 1, or 2;
R9 and R9a, at each occurrence, are independently selected from H, F, methyl, and ethyl;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94N(R19)xe2x80x94, xe2x80x94C(xe2x95x90O)NHxe2x80x94, or xe2x80x94NHC(xe2x95x90O)xe2x80x94;
Z is H, halo;
C1-C4 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
Ring B is selected from: 
R10 is H, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, S(xe2x95x90O)2R17;
C1-C6 alkyl substituted with 0-2 R10a;
C6-C10 aryl substituted with 0-4 R10b;
C3-C10 carbocycle substituted with 0-3 R10b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is optionally substituted with 0-3 R10b;
R10a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3, or aryl substituted with 0-4 R10b;
R10b, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R11, at each occurrence, is independently selected from H, C1-C4 alkoxy, C1, F, Br, I, xe2x95x90O, CN, NO2, NR18R19, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, CF3;
C1-C6 alkyl substituted with 0-1 R11a;
C6-C10 aryl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R11a, at each occurrence, is independently selected from H, C1xe2x80x94C6 alkyl, OR14, C1, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C10 carbocycle substituted with 0-3 R11b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R11b;
R11b, at each occurrence, is independently selected from H, OH, C1, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, benzyl, benzoyl, C(xe2x95x90O)CH3, t-butoxycarbonyl, and 3,5-dimethyl-isoxazole-S(xe2x95x90O)2xe2x80x94;
R12 at each occurrence, is independently selected from H, OH, C1, F, Br, I, CN, NO2, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, C1-C6 alkyl, and C2-C6 alkoxyalkyl;
R15, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R16, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR15R16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl;
R17 is H, C1-C6 alkyl, or C2-C6 alkoxyalkyl,
aryl substituted by 0-4 R17a, or
aryl-CH2xe2x80x94 wherein said aryl is substituted by by 0-4 R17a;
R17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, xe2x80x94OH, F, Cl, Br, I, CF3, OCF3, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, xe2x80x94NH2, xe2x80x94N(CH3)2, or C1-C4 haloalkyl;
R18, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R19, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR18R19 may be a heterocyclic ring selected from the group: piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; wherein said heterocyclic ring is substituted with 0-3 R11bxe2x80x94; and
R20 is H, OH, C1-C4 alkyl, phenyl, benzyl, or phenethyl.
[5] In a preferred embodiment the present invention provides a compound of Formula (Ia): 
wherein:
Ring B is selected from: 
Q is Q1 or (C1-C3 alkyl)-Oxe2x80x94Q1;
Q1 is C1-C6 alkyl substituted with 0-3 R1a;
C2-C6 alkenyl substituted with 0-3 R1a;
C2-C6 alkynyl substituted with 0-3 R1a;
C3-C10 cycloalkyl substituted with 0-3 R1b;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, and (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94;
R2 is H, methyl, or ethyl;
R5 is H, OR14;
C1-C6 alkyl substituted with 0-3 R5b;
C2-C6 alkenyl substituted with 0-3 R5b;
C2-C6 alkynyl substituted with 0-3 R5b;
C3-C6 cycloalkyl substituted with 0-3 R5c;
C3-C6 carbocycle substituted with 0-3 R5c;
phenyl substituted with 0-3 R5c; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3R5c;
R5a is H, C1-C4 alkyl, or C2-C4 alkenyl;
alternatively, R5 and R5a may be combined to form a C4-C7 cycloalkyl ring;
R5b, at each occurrence, is independently selected from:
H, C1-C6 alkyl, CF3, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C2-C6 alkenyl, C2-C6 alkynyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94,
C3-C10 cycloalkyl substituted with 0-3 R5c;
C3-C10 carbocycle substituted with 0-3 R5c;
C6-C10 aryl substituted with 0-3 R5c; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R5c;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
W is xe2x80x94(CR8R8a)pxe2x80x94;
p is 0, 1, or 2;
R8 and R8a, at each occurrence, are independently selected from H, methyl, and ethyl;
X is a bond;
phenyl substituted with 0-3 RXb;
C3-C6 cyclolakyl substituted with 0-3 RXb; or
5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-2 RXb;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
Y is a bond or xe2x80x94(CR9R9a)txe2x80x94Vxe2x80x94(CR9R9a)uxe2x80x94;
t is 0, 1, or 2;
u is 0, 1, or 2;
R9 and R9a, at each occurrence, are independently selected from H, F, methyl, and ethyl;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94N(R19)xe2x80x94, xe2x80x94NHC(xe2x95x90O)xe2x80x94, or xe2x80x94C(xe2x95x90O)NHxe2x80x94;
Z is H, F, Cl, Br;
C1-C4 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
R10 is C(xe2x95x90O)R17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2R17;
C1-C6 alkyl substituted with 0-2 R10a;
phenyl substituted with 0-3 R10b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is optionally substituted with 0-3 R10b;
R10a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3, or aryl substituted with 0-3 R10b;
R10b, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R11, at each occurrence, is independently selected from H, xe2x95x90O, NR18R19, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, CF3;
C1-C6 alkyl substituted with 0-1 R11a;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b;
R11a, at each occurrence, is independently selected from H, C1-C4 alkyl, OR14, Cl, F, Br, xe2x95x90O, CN, NO2, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, benzyl, benzoyl, C(xe2x95x90O)CH3, t-butoxycarbonyl, and 3,5-dimethyl-isoxazole-S(xe2x95x90O)2xe2x80x94;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, C1-C6 alkyl, and C2-C6 alkoxyalkyl;
R15, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R16, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94, (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
alternatively, xe2x80x94NR15R16 may be a heterocyclic ring selected from the group piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; and
R17 is H, C1-C6 alkyl, or C2-C6 alkoxyalkyl,
aryl substituted by 0-4 R17a, or
aryl-CH2xe2x80x94 wherein said aryl is substituted by by 0-4 R17a;
R17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, xe2x80x94OH, F, Cl, Br, I, CF3, OCF3, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, xe2x80x94NH2, xe2x80x94N(CH3)2, or C1-C4 haloalkyl;
R18, at each occurrence, is independently selected from H, C1-C6 alkyl, phenyl, benzyl, phenethyl, (C1-C6 alkyl)-C(xe2x95x90O)xe2x80x94 and (C1-C6 alkyl)-S(xe2x95x90O)2xe2x80x94;
R19, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and
alternatively, xe2x80x94NR18R19 may be a heterocyclic ring selected from the group: piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; wherein said heterocyclic ring is substituted with 0-3 R11bxe2x80x94.
[6] In a preferred embodiment the present invention provides a compound of Formula (Ia) wherein:
Q is Q1;
Q1 is C1-C6 alkyl substituted with 0-3 R1a;
C2-C6 alkenyl substituted with 0-3 R1a;
C2-C6 alkynyl substituted with 0-3 R1a;
C3-C10 cycloalkyl substituted with 0-3 R1b;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, and (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94;
R2 is H, methyl, or ethyl;
R5 is H, OR14;
C1-C6 alkyl substituted with 0-3 R5b;
C2-C6 alkenyl substituted with 0-3 R5b; or
C2-C6 alkynyl substituted with 0-3 R5b;
R5a is H, methyl, ethyl, propyl, butyl, or C2-C4 alkenyl; alternatively, R5 and R5a may be combined to form a C4-C7 cycloalkyl ring;
R5b, at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, CF3, OR14, Cl, F, Br, I, xe2x95x90O, NR15R16,
C3-C7 cycloalkyl substituted with 0-3 R5c;
C3-C7 carbocycle substituted with 0-3 R5c;
phenyl substituted with 0-3 R5c; and
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R5c;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C4 alkyl, C1-C3 alkoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
W is xe2x80x94(CHR8)pxe2x80x94;
p is 0 or 1;
R8 is H, methyl, or ethyl;
X is a bond;
phenyl substituted with 0-2 RXb;
C5-C6 cycloalkyl substituted with 0-3 RXb; or
5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-2 RXb;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
Y is a bond, xe2x80x94Vxe2x80x94, xe2x80x94CH2xe2x80x94Vxe2x80x94, xe2x80x94Vxe2x80x94CH2xe2x80x94, or xe2x80x94CH2xe2x80x94Vxe2x80x94CH2xe2x80x94;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, or xe2x80x94N(R19)xe2x80x94;
Z is H, F, Cl, Br,
C1-C4 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
R10 is C(xe2x95x90O)R17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2R17;
C1-C6 alkyl substituted with 0-2 R10a;
phenyl substituted with 0-3 R10b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is optionally substituted with 0-3 R10b;
R10a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, C1, F, Br, I, xe2x95x90O, CN, NO2, NR15R16, CF3, or aryl substituted with 0-3 R10b;
R10b, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R11, at each occurrence, is independently selected from H, xe2x95x90O, NR18R19, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, xe2x80x94S(xe2x95x90O)2NR18R19, CF3;
C1-C6 alkyl substituted with 0-1 R11a;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, xe2x95x90O, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, C1-C2 haloalkoxy, benzyl, benzoyl, C(xe2x95x90O)CH3, t-butoxycarbonyl, and 3,5-dimethyl-isoxazole-S(xe2x95x90O)2xe2x80x94;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, C1-C4 alkyl, and C2-C4 alkoxyalkyl;
R15, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
R16, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, CH3CH2C(xe2x95x90O)xe2x80x94, CH3C(xe2x95x90O)xe2x80x94, CH3CH2OC(xe2x95x90O)xe2x80x94, CH3OC(xe2x95x90O)xe2x80x94, CH3CH2S(xe2x95x90O)2xe2x80x94 and CH3S(xe2x95x90O)2xe2x80x94;
R17 is H, C1-C4 alkyl, or C2-C4 alkoxyalkyl;
phenyl substituted by 0-2 R17a; or
benzyl substituted by 0-2 R17a;
R17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, xe2x80x94OH, F, Cl, Br, I, CF3, OCF3, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, xe2x80x94NH2, xe2x80x94N(CH3)2, or C1-C4 haloalkyl;
R18, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
R19, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, and butyl; and
alternatively, xe2x80x94NR18R19 may be a heterocyclic ring selected from the group: piperidinyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, homopiperidinyl, piperazinyl, and N-methylpiperizinyl; wherein said heterocyclic ring is substituted with 0-3 R11bxe2x80x94.
[7] In a preferred embodiment the present invention provides a compound of Formula (Ia) wherein:
Q is Q1,
Q1 is C1-C6 alkyl substituted with 0-3 R1a;
C2-C6 alkenyl substituted with 0-3 R1a;
C2-C6 alkynyl substituted with 0-3 R1a;
C3-C6 cycloalkyl substituted with 0-3 R1b;
phenyl substituted with 0-3 R1b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C6 carbocycle substituted with 0-3 R1b;
phenyl substituted with 0-3 R1b; and
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, C1-C2 haloalkoxy, (methyl)OC(xe2x95x90O)xe2x80x94, (ethyl)OC(xe2x95x90O)xe2x80x94, (propyl)OC(xe2x95x90O)xe2x80x94, and (butyl)OC(xe2x95x90O)xe2x80x94;
R2 is H or methyl;
R5 is H, OR14;
C1-C4 alkyl substituted with 0-1 R5b;
C2-C4 alkenyl substituted with 0-1 R5b; or
C2-C4 alkynyl substituted with 0-1 R5b;
R5a is H, methyl, ethyl, propyl, or butyl;
alternatively, R5 and R5a may be combined to form a cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl ring;
R5b, at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, CF3, OR14, Cl, F, xe2x95x90O, NR15R16,
C3-C7 cycloalkyl substituted with 0-3 R5c;
C3-C7 carbocycle substituted with 0-3 R5c;
phenyl substituted with 0-3 R5c; and
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R5c; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
W is a bond, xe2x80x94CH2xe2x80x94, or xe2x80x94CH(CH3)xe2x80x94;
X is a bond;
phenyl substituted with 0-1 RXb;
C5-C6 cycloalkyl substituted with 0-1 RXb; or
5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-1 RXb; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, and isoxazolyl;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
Y is a bond, xe2x80x94Vxe2x80x94, xe2x80x94Vxe2x80x94CH2xe2x80x94, or xe2x80x94CH2Vxe2x80x94;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, or xe2x80x94N(R19)xe2x80x94;
Z is H, F, Cl, Br,
C1-C4 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
R11, at each occurrence, is independently selected from H, NR18R19, CF3;
C1-C4 alkyl substituted with 0-1 R11a;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, xe2x95x90O, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, NR15R16, CF3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
phenyl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
R13, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, methyl, ethyl, propyl, and butyl;
R15, at each occurrence, is independently selected from H, methyl, ethyl, propyl, or butyl;
R16, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
R18, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl and, phenethyl; and
R19, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and, phenethyl.
[8] In a preferred embodiment the present invention provides a compound of Formula (Ia) wherein:
Q is xe2x80x94CH3, xe2x80x94CH2CH3, xe2x80x94CH2CH2CH3, xe2x80x94CH2CH2CH2CH3, xe2x80x94CH2CH2CH2CH2CH3, xe2x80x94CH2CH2CH2CH2CH2CH3, xe2x80x94CH(CH3)2, xe2x80x94CH(CH3)CH2CH3, xe2x80x94CH2CH(CH3)2, xe2x80x94CH2C(CH3)3,
xe2x80x94CF3, xe2x80x94CH2CF3, xe2x80x94CH2CH2CF3, xe2x80x94CH2CH2CH2CF3,
xe2x80x94CHxe2x95x90CH2, xe2x80x94CH2CHxe2x95x90CH2, xe2x80x94CH2C(CH3)xe2x95x90CH2, xe2x80x94CH2CHxe2x95x90C(CH3)2, xe2x80x94CH2CH2CHxe2x95x90CH2, xe2x80x94CH2CH2C(CH3)xe2x95x90CH2, xe2x80x94CH2CH2CHxe2x95x90C(CH3)2, cis-CH2CHxe2x95x90CH(CH3), cis-CH2CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CH(CH3), trans-CH2CH2CHxe2x95x90CH(CH3);
xe2x80x94Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1C(CH3), cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclopropyl-CH2xe2x80x94, cyclobutyl-CH2xe2x80x94, cyclopentyl-CH2xe2x80x94, cyclohexyl-CH2xe2x80x94, cyclopropyl-CH2CH2xe2x80x94, cyclobutyl-CH2CH2xe2x80x94, cyclopentyl-CH2CH2xe2x80x94, cyclohexyl-CH2CH2xe2x80x94,
phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-, 4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-, phenyl-CH2xe2x80x94, (2-F-phenyl)CH2xe2x80x94, (3-F-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2xe2x80x94, (2-Cl-phenyl)CH2xe2x80x94, (3-Cl-phenyl)CH2xe2x80x94, (4-Cl-phenyl)CH2xe2x80x94,
(2,3-diF-phenyl)CH2xe2x80x94, (2,4-diF-phenyl)CH2xe2x80x94, (2,5-diF-phenyl)CH2xe2x80x94, (2,6-diF-phenyl)CH2xe2x80x94, (3,4-diF-phenyl)CH2xe2x80x94, (3,5-diF-phenyl)CH2xe2x80x94, (2,3-diCl-phenyl)CH2xe2x80x94, (2,4-diCl-phenyl)CH2xe2x80x94, (2,5-diCl-phenyl)CH2xe2x80x94, (2,6-diCl-phenyl)CH2xe2x80x94, (3,4-diCl-phenyl)CH2xe2x80x94, (3,5-diCl-phenyl)CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2xe2x80x94, (3-Cl-4-F-phenyl)CH2xe2x80x94,
2-furanyl-CH2xe2x80x94, 3-furanyl-CH2xe2x80x94, 2-thienyl-CH2xe2x80x94, 3-thienyl-CH2xe2x80x94, 2-pyridyl-CH2xe2x80x94, 3-pyridyl-CH2xe2x80x94, 4-pyridyl-CH2xe2x80x94, 1-imidazolyl-CH2xe2x80x94, 2-oxazolyl-CH2xe2x80x94, 4-oxazolyl-CH2xe2x80x94, 5-oxazolyl-CH2xe2x80x94, 3-isoxazolyl-CH2xe2x80x94, 4-isoxazolyl-CH2xe2x80x94, 5-isoxazolyl-CH2xe2x80x94,
phenyl-CH2CH2xe2x80x94, (2-F-phenyl)CH2CH2xe2x80x94, (3-F-phenyl)CH2CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, (2-Cl-phenyl)CH2CH2xe2x80x94, (3-Cl-phenyl)CH2CH2xe2x80x94, (4-Cl-phenyl)CH2CH2xe2x80x94, (2,3-diF-phenyl)CH2CH2xe2x80x94, (2,4-diF-phenyl)CH2CH2xe2x80x94, (2,5-diF-phenyl)CH2CH2xe2x80x94, (2,6-diF-phenyl)CH2CH2xe2x80x94, (3,4-diF-phenyl)CH2CH2xe2x80x94, (3,5-diF-phenyl)CH2CH2xe2x80x94, (2,3-diCl-phenyl)CH2CH2xe2x80x94, (2,4-diCl-phenyl)CH2CH2xe2x80x94, (2,5-diCl-phenyl)CH2CH2xe2x80x94, (2,6-diCl-phenyl)CH2CH2xe2x80x94, (3,4-diCl-phenyl)CH2CH2xe2x80x94, (3,5-diCl-phenyl)CH2CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2CH2xe2x80x94;
furanyl-CH2CH2xe2x80x94, thienyl-CH2CH2xe2x80x94, pyridyl-CH2CH2xe2x80x94, 1-imidazolyl-CH2CH2xe2x80x94, oxazolyl-CH2CH2xe2x80x94, isoxazolyl-CH2CH2xe2x80x94, 3,5-dimethylisoxazol-4-yl-CH2CH2xe2x80x94, phenyl-propyl-;
benzyl-CH(NH2)xe2x80x94, benzyl-CH(NHC(xe2x95x90O)xe2x80x94O-tBu)-, benzyloxy-CH2xe2x80x94, pyrrolidin-2-yl-, or 3-t-butoxycarbonylpyrrolidin-2-yl-;
R2 is H or methyl;
R5 is xe2x80x94CH3, xe2x80x94CH2CH3, xe2x80x94CH2CH2CH3, xe2x80x94CH(CH3)2, xe2x80x94CH2CH2CH2CH3, xe2x80x94CH(CH3)CH2CH3, xe2x80x94CH2CH(CH3)2, xe2x80x94CH2C(CH3)3, xe2x80x94CH2CH2CH2CH2CH3, xe2x80x94CH(CH3)CH2CH2CH3, xe2x80x94CH2CH(CH3)CH2CH3, xe2x80x94CH2CH2CH(CH3)2, xe2x80x94CH(CH2CH3)2,
xe2x80x94CF3, xe2x80x94CH2CF3, xe2x80x94CH2CH2CF3, xe2x80x94CH2CH2CH2CF3, xe2x80x94CH2CH2CH2CH2CF3,
xe2x80x94CHxe2x95x90CH2, xe2x80x94CH2CHxe2x95x90CH2, xe2x80x94CH2CH2CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CHCH3, cis-CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CH(C6H5), xe2x80x94CH2CHxe2x95x90C(CH3)2, cis-CH2CHxe2x95x90CHCH2CH3, trans-CH2CHxe2x95x90CHCH2CH3, cis-CH2CH2CHxe2x95x90CH(CH3), trans-CH2CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CHCH2(C6H5),
xe2x80x94Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1C(CH3), xe2x80x94CH2Cxe2x89xa1C(C6H5), xe2x80x94CH2CH2Cxe2x89xa1CH, xe2x80x94CH2CH2Cxe2x89xa1C(CH3), xe2x80x94CH2CH2Cxe2x89xa1C(C6H5), xe2x80x94CH2CH2CH2Cxe2x89xa1CH, xe2x80x94CH2CH2CH2Cxe2x89xa1C(CH3), xe2x80x94CH2CH2CH2Cxe2x89xa1C(C6H5),
cyclopropyl-CH2xe2x80x94, cyclobutyl-CH2xe2x80x94, cyclopentyl-CH2xe2x80x94, cyclohexyl-CH2xe2x80x94, (2-CH3-cyclopropyl)CH2xe2x80x94, (3-CH3-cyclobutyl)CH2xe2x80x94, cyclopropyl-CH2CH2xe2x80x94, cyclobutyl-CH2CH2xe2x80x94, cyclopentyl-CH2CH2xe2x80x94, cyclohexyl-CH2CH2xe2x80x94, (2-CH3-cyclopropyl)CH2CH2xe2x80x94, 3-CH3-cyclobutyl)CH2CH2xe2x80x94,
phenyl-CH2xe2x80x94, (2-F-phenyl)CH2xe2x80x94, (3-F-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2xe2x80x94, (3,5-diF-phenyl)CH2xe2x80x94, 2-furanyl-CH2xe2x80x94, 3-furanyl-CH2xe2x80x94, 2-thienyl-CH2xe2x80x94, 3-thienyl-CH2xe2x80x94, 2-pyridyl-CH2xe2x80x94, 3-pyridyl-CH2xe2x80x94, 4-pyridyl-CH2xe2x80x94, 1-imidazolyl-CH2xe2x80x94, 2-oxazolyl-CH2xe2x80x94, 4-oxazolyl-CH2xe2x80x94, 5-oxazolyl-CH2xe2x80x94, 3-isoxazolyl-CH2xe2x80x94, 4-isoxazolyl-CH2xe2x80x94, 5-isoxazolyl-CH2xe2x80x94,
phenyl-CH2CH2xe2x80x94, (2-F-phenyl)CH2CH2xe2x80x94, (3-F-phenyl)CH2CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, furanyl-CH2CH2xe2x80x94, thienyl-CH2CH2xe2x80x94, pyridyl-CH2CH2xe2x80x94, 1-imidazolyl-CH2CH2xe2x80x94, oxazolyl-CH2CH2xe2x80x94, isoxazolyl-CH2CH2xe2x80x94;
methoxy, ethoxy, propoxy, or butoxy;
R5a is H;
alternatively, R5 and R5a may be combined to form cyclopentyl, cyclohexyl, or cycloheptyl;
W is a bond, xe2x80x94CH2xe2x80x94, or xe2x80x94CH(CH3)xe2x80x94;
X is a bond; 
Y is a bond, xe2x80x94CH2xe2x80x94Vxe2x80x94, xe2x80x94Vxe2x80x94, or xe2x80x94Vxe2x80x94CH2xe2x80x94;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94NHxe2x80x94, or xe2x80x94N(CH3)xe2x80x94;
Z is H, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl,
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF3O-phenyl, 3-CF3O-phenyl, 4-CF3O-phenyl,
furanyl, thienyl, pyridyl, N-oxide-pyridinyl, 2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl, morpholino, N-piperinyl,
phenyl-CH2xe2x80x94, (2-F-phenyl)CH2xe2x80x94, (3-F-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2xe2x80x94, (2-Cl-phenyl)CH2xe2x80x94, (3-Cl-phenyl)CH2xe2x80x94, (4-Cl-phenyl)CH2xe2x80x94, (2,3-diF-phenyl)CH2xe2x80x94, (2,4-diF-phenyl)CH2xe2x80x94, (2,5-diF-phenyl)CH2xe2x80x94, (2,6-diF-phenyl)CH2xe2x80x94, (3,4-diF-phenyl)CH2xe2x80x94, (3,5-diF-phenyl)CH2xe2x80x94, (2,3-diCl-phenyl)CH2xe2x80x94, (2,4-diCl-phenyl)CH2xe2x80x94, (2,5-diCl-phenyl)CH2xe2x80x94, (2,6-diCl-phenyl)CH2xe2x80x94, (3,4-diCl-phenyl)CH2xe2x80x94, (3,5-diCl-phenyl)CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2xe2x80x94, (3-Cl-4-F-phenyl)CH2xe2x80x94, (2-MeO-phenyl)CH2xe2x80x94, (3-MeO-phenyl)CH2xe2x80x94, (4-MeO-phenyl)CH2xe2x80x94, (2-PhO-phenyl)CH2xe2x80x94, (3-PhO-phenyl)CH2xe2x80x94, (4-PhO-phenyl)CH2xe2x80x94, (2-Me-phenyl)CH2xe2x80x94, (3-Me-phenyl)CH2xe2x80x94, (4-Me-phenyl)CH2xe2x80x94, (2-MeS-phenyl)CH2xe2x80x94, (3-MeS-phenyl)CH2xe2x80x94, 4-MeS-phenyl)CH2xe2x80x94, (2-CF3O-phenyl)CH2xe2x80x94, (3-CF3O-phenyl)CH2xe2x80x94, (4-CF3O-phenyl)CH2xe2x80x94, (furanyl)CH2xe2x80x94, (thienyl)CH2xe2x80x94, (pyridyl)CH2xe2x80x94, (2-Me-pyridyl)CH2xe2x80x94, (3-Me-pyridyl)CH2xe2x80x94, (4-Me-pyridyl)CH2xe2x80x94, (1-imidazolyl)CH2xe2x80x94, (oxazolyl)CH2xe2x80x94, (isoxazolyl)CH2xe2x80x94, (1-benzimidazolyl)CH2xe2x80x94, (cyclopropyl)CH2xe2x80x94, (cyclobutyl)CH2xe2x80x94, (cyclopentyl)CH2xe2x80x94, (cyclohexyl)CH2xe2x80x94, (morpholino)CH2xe2x80x94, (N-pipridinyl)CH2xe2x80x94,
phenyl-CH2CH2xe2x80x94, (phenyl)2CHCH2xe2x80x94, (2-F-phenyl)CH2CH2xe2x80x94, (3-F-phenyl)CH2CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, (2-Cl-phenyl)CH2CH2xe2x80x94, (3-Cl-phenyl)CH2CH2xe2x80x94, (4-Cl-phenyl)CH2CH2xe2x80x94, (2,3-diF-phenyl)CH2CH2xe2x80x94, (2,4-diF-phenyl)CH2CH2xe2x80x94, (2,5-diF-phenyl)CH2CH2xe2x80x94, (2,6-diF-phenyl)CH2CH2xe2x80x94, (3,4-diF-phenyl)CH2CH2xe2x80x94, (3,5-diF-phenyl)CH2CH2xe2x80x94, (2,3-diCl-phenyl)CH2CH2xe2x80x94, (2,4-diCl-phenyl)CH2CH2xe2x80x94, (2,5-diCl-phenyl)CH2CH2xe2x80x94, (2,6-diCl-phenyl)CH2CH2xe2x80x94, (3,4-diCl-phenyl)CH2CH2xe2x80x94, (3,5-diCl-phenyl)CH2CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2CH2xe2x80x94, (3-Cl-4-F-phenyl)CH2CH2xe2x80x94, (2-MeO-phenyl)CH2CH2xe2x80x94, (3-MeO-phenyl)CH2CH2xe2x80x94, (4-MeO-phenyl)CH2CH2xe2x80x94, (2-Me-phenyl)CH2CH2xe2x80x94, (3-Me-phenyl)CH2CH2xe2x80x94, (4-Me-phenyl)CH2CH2xe2x80x94, (2-MeS-phenyl)CH2CH2xe2x80x94, (3-MeS-phenyl)CH2CH2xe2x80x94, (4-MeS-phenyl)CH2CH2xe2x80x94, (2-CF3O-phenyl)CH2CH2xe2x80x94, (3-CF3O-phenyl)CH2CH2xe2x80x94, (4-CF3O-phenyl)CH2CH2xe2x80x94, (furanyl)CH2CH2xe2x80x94, (thienyl)CH2CH2xe2x80x94, (pyridyl)CH2CH2xe2x80x94, (2-Me-pyridyl)CH2CH2xe2x80x94, (3-Me-pyridyl)CH2CH2xe2x80x94, (4-Me-pyridyl)CH2CH2xe2x80x94, (imidazolyl)CH2CH2xe2x80x94, (oxazolyl)CH2CH2xe2x80x94, (isoxazolyl)CH2CH2xe2x80x94, (benzimidazolyl)CH2CH2xe2x80x94, (cyclopropyl)CH2CH2xe2x80x94, (cyclobutyl)CH2CH2xe2x80x94, (cyclopentyl)CH2CH2xe2x80x94, (cyclohexyl)CH2CH2xe2x80x94, (morpholino)CH2CH2xe2x80x94, or (N-pipridinyl)CH2CH2xe2x80x94;
R11, at each occurrence, is independently selected from H, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, 2-F-phenyl-, 3-F-phenyl, 4-F-phenyl, 4-Cl-phenyl, 4-CH3-phenyl, 4-MeO-phenyl-, 4-CF3-phenyl, (4-F-phenyl)CH2xe2x80x94, (4-Cl-phenyl)CH2xe2x80x94, (4-CH3-phenyl)CH2xe2x80x94, (4-CF3-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, (4-Cl-phenyl)CH2CH2xe2x80x94, (4-CH3-phenyl)CH2CH2xe2x80x94, (4-CF3-phenyl)CH2CH2xe2x80x94, pyridin-2-yl-, pyridin-3-yl-, 4-CF3-pyridin-2-yl-, 4-CH3-pyridin-2-yl-, thiazol-2-yl-, azapan-1-yl, N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, and N,N-dibutylamino; and
R13, at each occurrence, is independently selected from H, MeO, F, and Cl.
[9] In a preferred embodiment the present invention provides a compound of Formula of Formula (Ic); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[10] In a preferred embodiment the present invention provides a compound of Formula (Id); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[11] In a preferred embodiment the present invention provides a compound of Formula (Ie): 
or a pharmaceutically acceptable salt form or prodrug thereof.
[12] In a preferred embodiment the present invention provides a compound selected from:
3-(2(R)-Cyclopentylmethyl-3(S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Cyclopentylmethyl-3(S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-(4-fluoro-phenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Benzyl-3(S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isopropyl-3(S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Cyclopentylmethyl-3(S)-hydroxyl-1-oxo-4-(3,5-difluorophenoxy)butyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-4-(3,5-difluorophenoxy)butyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Cyclopentymethyl-3(S)-hydroxyl-1-oxo-4-phenoxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-4-phenoxybutyl)amino-7-chloro-1-methyl-5-(4-fluoro phenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-4-cyclohexyloxybutyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-4-cyclohexyloxybutyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-4-phenoxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-4-phenoxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Benzyl-3(S)-hydroxyl-1-oxo-4-cyclohexyloxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Cyclopentylmethyl-3(S)-hydroxyl-1-oxo-4-cyclohexyloxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-4-cyclohexyloxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isopropyl-3(S)-hydroxyl-1-oxo-4-cyclohexyloxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methoxy-3(S)-hydroxyl-1-oxo-4-(4-trifluoromethylbenzyloxy)butyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-4-(2,4-difluorobenzyloxy)butyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Vinyl-3(S)-hydroxyl-1-oxo-4-benzyloxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-4-cyclohexyloxybutyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-3-cyclopropylpropyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-heptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R)-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-heptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-heptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-nonyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-hexyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-4-phenylbutyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-6-phenylhexyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-butyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Isobutyl-3(S)-hydroxyl-1-oxo-octyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-heptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-3-phenylpropyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-5,5-dimethylhexyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-hexyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2(R)-Methyl-3(S)-hydroxyl-1-oxo-3-(4-propoxyphenyl)propyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
2-(R)-cyclopropylmethyl-3-(S)-hydroxylheptanoic acid (2-oxo-1-(3-phenoxybenzyl)azapan-3-(S)-yl)amide;
2(R)-cyclopropylmethyl-5-(3,5-difluorophenyl)-3-(S)-hydroxypentanoic acid (2-oxo-1-(3-phenoxybenzyl)azapan-3-(S)-yl)amide;
4-cyclopentyl-2-(R)-cyclopropylmethyl-3-(S)-hydroxybutanoic acid (2-oxo-1-(3-phenoxybenzyl)azapan-3-(S)-yl)amide;
2-(R)-cyclopropylmethyl-3-(S)-hydroxyheptanioc acid (1-(5-bromo-3-pyridinyl)methyl-2-oxo-azapan-3-(S)-yl)amide;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(azapan-1-yl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-5-(3,5-difluorophenyl)-3(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-(pyridn-2-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-(4-chlorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(4-methoxyphenyl)1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(4-methoxyphenyl)-1-methyl-2,3-dihydro-H-1,4-benxodiazepin-2-one;
3-(S)-(4-cyclopentyl-2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxobutyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxohept-6-enyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxohept-6-enyl)amino-1-methyl-5-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-cyclopropylmethyl-5-(3,5-dimethylisoxazol-4-yl)-3-(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-(pyridin-2-yl)-2,3-dihydro-1H-1,4 benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(4-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifouoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(5-cyclopentyl-2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-(pyridin-2-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-iso-butyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxo-5-(thiophen-2-yl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-cyclopropylmethyl-5-(furan-2-yl)3-(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(5-cyclopentyl-2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxopentyl)amino-5-(4-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-cyclopropylmethyl-5-(3,5-difluorophenyl)-3-(S)-hydroxy-1-oxopentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(3-(S)-hydroxyl-2-(R)-(thiophen-2-yl)methyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-7-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-7-methoxy-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-cyclobutylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-(3,5-difluorobenzyl)-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydor-1H-1,4-benzodiaxepin-2-one;
3-(S)-(2-(R)-(furan-2-yl)methyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxl-1-oxo-5-pheylpentyl)amino-1-methyl-5-(pyridin-2-yl)-2,3-dihydro-1H-benzodiazepin-2-one;
3-(2-(R)-iso-butyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(4-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-iso-butyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(4-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-5-(furan-2-yl)-3-(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(5-cyclopentyl-2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxopentyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxooctyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxononyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethyl(pyridin-2-yl))-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclobutylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(40trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopentylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-methyl-2-pyridiyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-methyl-2-pyridyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxobutyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-(3-butenyl)-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-(3-methylbutyl)3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-ethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-propyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1,4-benzodiazepin-2-one;
3-(S)-(2-(R)-butyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(4-(S)-amino-3-(R)-hydroxyl-2-(R)-methyl-1-oxo-5-phenylpentyl)amino-7-chloro-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(4-(S)-(tert-butoxycarbonylamino-3-(R)-hydroxyl-2-(R)-methyl-1-oxo-5-phenylpentyl)amino-7-chloro-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(3-(tert-butoxycarbonylpyrrolidin-2-(R)-yl)-3-(R)-hydroxyl-2-(R)-methyl-1-oxopropyl)amino-7-chloro-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(3-(R)-hydroxyl-2-(R)-methyl-1-oxo-3-(pyrrolidin-2-(R)-yl)propyl)-amino-7-chloro-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(4-benzyloxy-3-(R)-hydroxyl-2-(R)-iso-propyl-1-oxobutylamino-7-chloro-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
2-(4-(S)-amino-3-(S)-hydroxyl-2-(S)-methyl-1-oxo-5-phenylpentyl)amino-7-chloro-5-(2-flourophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
2-(4-(S)-(tert-butoxycarbonylamino-3-(S)hydroxyl-2-(S)-methyl-1-oxo-5-phenylpentyl)amino-7-chloro-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(thiazol-2-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-cyclopropylmethyl-5-(thiazol-2-yl)-2,3-dihydro-1H-1,4benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-cyclopropylmethyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-benzyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(3-phenoxybenzyl)-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(3-pyridinylmethyl)-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(S)-cyclopropylmethyl-3-(R)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(S)-cyclopropylmethyl-3-(R)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(R)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(S)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(S)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-3-(S)-methyl-1-oxoheptyl)amino-1-methyl-5-(4-trifluoromethyl-phenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(3-phenoxybenzyl)-5-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmehtyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-benzyl-5-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(3-(S)-acetoxy-2-(R)-iso-butyl-1-oxoheptyl)amino-5-(4-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(S)-(5-cyclopentyl-2-(R)-cyclopropylmethyl-3-(S)-methoxy-1-oxopentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
1-(1-hydroxypentyl)cyclohexanecarboxylic acid(5-(4-fluorophenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)amide;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxooctyl)amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxononyl)amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one;
3-(2-(R)-cyclopropylmethyl-5-(furan-2-yl)-3-(S)-hydroxyl-1-oxopentyl)amino-5-methyl-5H,7H-dibenzo[b,d]azepin-6-one;
2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-heptanoic acid (2-oxo-1-(3-phenylamino-benzyl)azapan-3-(S)-yl)amide;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-cyclopentyl-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-benzyl-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-benzyl-1-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-cycloheptyl-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cycloropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-benzyl-5-cycloheptyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-butyl-5-cycloheptyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(2-pyridinylmethyl)-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(3-pyridinylmethyl)-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(S)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxopentyl)amino-1-(3-pyridynylmethyl)-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-1(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(N,N-dibutylamino)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-n-butyl-5-t-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(2-oxo-3,3-dimethylbutyl)-5-n-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-benzyl-5-t-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(2-picolyl)-5-n-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-Isobutyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-homopiperidino-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-1,3-dioxoheptyl)amino-1-methyl-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one; and
1-pentyrylcyclohexanecarboxylic acid (5-(4-fluorophenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)amide.
[13] In a preferred embodiment the present invention provides a compound of Formula (I) wherein the stereochemistry of carbon 3 in lactam ring B is of the S configuration.
[14] In a preferred embodiment the present invention provides a compound of Formula (I) wherein the stereochemistry of carbon 3 in lactam ring B is of the R configuration.
[15] In a preferred embodiment the present invention provides a compound of Formula (Ib) 
wherein:
Ring B is selected from: 
Q1 is C1-C6 alkyl substituted with 0-3 R1a;
C2-C6 alkenyl substituted with 0-3 R1a;
C2-C6 alkynyl substituted with 0-3 R1a;
C3-C10 cycloalkyl substituted with 0-3 R1b;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, C1-C6 alkyl, OR14, Cl, F. Br, I , NR15R16, CF3;
C3-C10 carbocycle substituted with 0-3 R1b;
C6-C10 aryl substituted with 0-3 R1b; and
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 haloalkyl-Sxe2x80x94, and (C1-C6 alkyl)-Oxe2x80x94C(xe2x95x90O)xe2x80x94;
R5 is OR14xe2x80x94;
C1-C6 alkyl substituted with 0-3 R5b;
C2-C6 alkenyl substituted with 0-3 R5b; or
C2-C6 alkynyl substituted with 0-3 R5b;
R5a is H, methyl, ethyl, propyl, butyl, or C2-C4 alkenyl;
alternatively, R5 and R5a may be combined to form a C4-C7 cycloalkyl ring;
R5b, at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, CF3, OR14, Cl, F, Br, I, xe2x95x90O, NR15R16,
C3-C7 cycloalkyl substituted with 0-3 R5c;
C3-C7 carbocycle substituted with 0-3 R5c;
phenyl substituted with 0-3 R5c; and
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R5c;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C4 alkyl, C1-C3 alkoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
W is xe2x80x94(CHR8)pxe2x80x94;
p is 0 or 1;
R8 is H, methyl, or ethyl;
X is a bond;
phenyl substituted with 0-2 RXb;
C5-C6 cycloalkyl substituted with 0-3 RXb; or
5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-2 RXb;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
Y is a bond, xe2x80x94Vxe2x80x94, xe2x80x94CH2xe2x80x94Vxe2x80x94, xe2x80x94Vxe2x80x94CH2xe2x80x94, or xe2x80x94CH2xe2x80x94Vxe2x80x94CH2xe2x80x94;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, or xe2x80x94N(R19)xe2x80x94;
Z is H, F, Cl, Br, C1-C4 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
R11, at each occurrence, is independently selected from H, xe2x95x90O, NR18R19, C(xe2x95x90O)R17, C(xe2x95x90O)OR17, C(xe2x95x90O)NR18R19, S(xe2x95x90O)2NR18R19, CF3;
C1-C6 alkyl substituted with 0-1 R11a;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, xe2x95x90O, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
C6-C10 aryl substituted with 0-4 R12b;
C3-C10 carbocycle substituted with 0-4 R12b; or
5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R12b;
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, C1-C6 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, and C1-C4 haloalkyl-Sxe2x80x94;
R13, at each occurrence, is independently selected from H, OH, C1-C6 alkyl, C1-C4 alkoxy, Cl, F, Br, I, CN, NO2, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, C1-C4 alkyl, and C2-C4 alkoxyalkyl;
R15, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
R16, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl, CH3CH2C(xe2x95x90O)xe2x80x94, CH3C(xe2x95x90O)xe2x80x94, CH3CH2OC(xe2x95x90O)xe2x80x94, CH3OC(xe2x95x90O)xe2x80x94, CH3CH2S(xe2x95x90O)2xe2x80x94 and CH3S(xe2x95x90O)2xe2x80x94;
R17 is H, phenyl, benzyl, C1-C4 alkyl, or C2-C4 alkoxyalkyl;
R18, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and
R19, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, and butyl.
[16] In a preferred embodiment the present invention provides a compound of Formula (Ib)
Q1 is C1-C6 alkyl substituted with 0-3 R1a;
C2-C6 alkenyl substituted with 0-3 R1a;
C2-C6 alkynyl substituted with 0-3 R1a;
C3-C6 cycloalkyl substituted with 0-3 R1b;
phenyl substituted with 0-3 R1b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R1b;
R1a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, OR14, Cl, F, Br, I, NR15R16, CF3;
C3-C6 carbocycle substituted with 0-3 R1b;
phenyl substituted with 0-3 R1b; and
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R1b;
R1b, at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO2, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, C1-C2 haloalkoxy, (methyl)OC(xe2x95x90O)xe2x80x94, (ethyl)OC(xe2x95x90O)xe2x80x94, (propyl)OC(xe2x95x90O)xe2x80x94, and (butyl)OC(xe2x95x90O)xe2x80x94;
R5 is OR14;
C1-C4 alkyl substituted with 0-1 R5b;
C2-C4 alkenyl substituted with 0-1 R5b; or
C2-C4 alkynyl substituted with 0-1 R5b;
R5a is H, methyl, ethyl, propyl, or butyl;
alternatively, R5 and R5a may be combined to form a cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl ring;
R5b, at each occurrence, is independently selected from:
H, methyl, ethyl, propyl, butyl, CF3, OR14, Cl, F, xe2x95x90O, NR15R16,
C3-C7 cycloalkyl substituted with 0-3 R5c;
C3-C7 carbocycle substituted with 0-3 R5c;
phenyl substituted with 0-3 R5c; and
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R5c; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R5c, at each occurrence, is independently selected from H, OH, Cl, F, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
W is a bond, xe2x80x94CH2xe2x80x94, or xe2x80x94CH(CH3)xe2x80x94;
X is a bond;
phenyl substituted with 0-1 RXb;
C5-C6 cycloalkyl substituted with 0-1 RXb; or
5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-1 RXb; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, and isoxazolyl;
RXb, at each occurrence, is independently selected from H, OH, Cl, F, Br, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
Y is a bond, xe2x80x94Vxe2x80x94, xe2x80x94Vxe2x80x94CH2xe2x80x94, or xe2x80x94CH2Vxe2x80x94;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, or xe2x80x94N(R19)xe2x80x94;
Z is H, F, Cl, Br,
C1-C4 alkyl substituted with 0-2 R12;
C2-C4 alkenyl substituted with 0-2 R12;
C2-C4 alkynyl substituted with 0-2 R12;
C6-C10 aryl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b;
R11, at each occurrence, is independently selected from H, NR18R19, CF3;
C1-C4 alkyl substituted with 0-1 R11a;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, xe2x95x90O, NR15R16, CF3;
phenyl substituted with 0-3 R11b;
C3-C6 carbocycle substituted with 0-3 R11b; or
5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R11b; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
R11b, at each occurrence, is independently selected from H, OH, Cl, F, NR15R16, CF3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
R12 at each occurrence, is independently selected from H, OH, Cl, F, Br, NR15R16, xe2x80x94C(xe2x95x90O)NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, nethoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
phenyl substituted with 0-4 R12b;
C3-C6 carbocycle substituted with 0-4 R12b; or
5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R12b
R12b, at each occurrence, is independently selected from H, OH, Cl, F, Br, NR15R16, CF3, acetyl, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C1-C2 haloalkyl, and C1-C2 haloalkoxy;
R13, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br, CN, NR15R16, and CF3;
R14, at each occurrence, is independently selected from H, phenyl, benzyl, methyl, ethyl, propyl, and butyl;
R15, at each occurrence, is independently selected from H, methyl, ethyl, propyl, or butyl;
R16, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
R18, at each occurrence, is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl and, phenethyl; and
R19, at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl and, phenethyl.
[17] In a preferred embodiment the present invention provides a compound of Formula (Ib) wherein:
Q1 is xe2x80x94CH3, xe2x80x94CH2CH3, xe2x80x94CH2CH2CH3, xe2x80x94CH2CH2CH2CH3, xe2x80x94CH2CH2CH2CH2CH3, xe2x80x94CH2CH2CH2CH2CH2CH3, xe2x80x94CH(CH3)2, xe2x80x94CH(CH3)CH2CH3, xe2x80x94CH2CH(CH3)2, xe2x80x94CH2C(CH3)3,
xe2x80x94CF3, xe2x80x94CH2CF3, xe2x80x94CH2CH2CF3, xe2x80x94CH2CH2CH2CF3, xe2x80x94CHxe2x95x90CH2, xe2x80x94CH2CHxe2x95x90CH2, xe2x80x94CH2C(CH3)xe2x95x90CH2, xe2x80x94CH2CHxe2x95x90C(CH3)2, xe2x80x94CH2CH2CHxe2x95x90CH2, xe2x80x94CH2CH2C(CH3)xe2x95x90CH2, xe2x80x94CH2CH2CHxe2x95x90C(CH3)2, cis-CH2CHxe2x95x90CH(CH3), cis-CH2CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CH(CH3), trans-CH2CH2CHxe2x95x90CH(CH3);
xe2x80x94Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1C(CH3),
cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl-, cyclopropyl-CH2xe2x80x94, cyclobutyl-CH2xe2x80x94, cyclopentyl-CH2xe2x80x94, cyclohexyl-CH2xe2x80x94, cyclopropyl-CH2CH2xe2x80x94, cyclobutyl-CH2CH2xe2x80x94, cyclopentyl-CH2CH2xe2x80x94, cyclohexyl-CH2CH2xe2x80x94,
phenyl-, 2-F-phenyl-, 3-F-phenyl-, 4-F-phenyl-, 4-methoxyphenyl-, 4-ethoxyphenyl-, 4-propoxyphenyl-, phenyl-CH2xe2x80x94, (2-F-phenyl)CH2xe2x80x94, (3-F-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2xe2x80x94, (2-Cl-phenyl)CH2xe2x80x94, (3-Cl-phenyl)CH2xe2x80x94, (4-Cl-phenyl)CH2xe2x80x94,
(2,3-diF-phenyl)CH2xe2x80x94, (2,4-diF-phenyl)CH2xe2x80x94, (2,5-diF-phenyl)CH2xe2x80x94, (2,6-diF-phenyl)CH2xe2x80x94, (3,4-diF-phenyl)CH2xe2x80x94, (3,5-diF-phenyl)CH2xe2x80x94, (2,3-diCl-phenyl)CH2xe2x80x94, (2,4-diCl-phenyl)CH2xe2x80x94, (2,5-diCl-phenyl)CH2xe2x80x94, (2,6-diCl-phenyl)CH2xe2x80x94, (3,4-diCl-phenyl)CH2xe2x80x94, (3,5-diCl-phenyl)CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2xe2x80x94, (3-Cl-4-F-phenyl)CH2xe2x80x94,
2-furanyl-CH2xe2x80x94, 3-furanyl-CH2xe2x80x94, 2-thienyl-CH2xe2x80x94, 3-thienyl-CH2xe2x80x94, 2-pyridyl-CH2xe2x80x94, 3-pyridyl-CH2xe2x80x94, 4-pyridyl-CH2xe2x80x94, 1-imidazolyl-CH2xe2x80x94, 2-oxazolyl-CH2xe2x80x94, 4-oxazolyl-CH2xe2x80x94, 5-oxazolyl-CH2xe2x80x94, 3-isoxazolyl-CH2xe2x80x94, 4-isoxazolyl-CH2xe2x80x94, 5-isoxazolyl-CH2xe2x80x94,
phenyl-CH2CH2xe2x80x94, (2-F-phenyl)CH2CH2xe2x80x94, (3-F-phenyl)CH2CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, (2-Cl-phenyl)CH2CH2xe2x80x94, (3-Cl-phenyl)CH2CH2xe2x80x94, (4-Cl-phenyl)CH2CH2xe2x80x94, (2,3-diF-phenyl)CH2CH2xe2x80x94, (2,4-diF-phenyl)CH2CH2xe2x80x94, (2,5-diF-phenyl)CH2CH2xe2x80x94, (2,6-diF-phenyl)CH2CH2xe2x80x94, (3,4-diF-phenyl)CH2CH2xe2x80x94, (3,5-diF-phenyl)CH2CH2xe2x80x94, (2,3-diCl-phenyl)CH2CH2xe2x80x94, (2,4-diCl-phenyl)CH2CH2xe2x80x94, (2,5-diCl-phenyl)CH2CH2xe2x80x94, (2,6-diCl-phenyl)CH2CH2xe2x80x94, (3,4-diCl-phenyl)CH2CH2xe2x80x94, (3,5-diCl-phenyl)CH2CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2CH2xe2x80x94;
furanyl-CH2CH2xe2x80x94, thienyl-CH2CH2xe2x80x94, pyridyl-CH2CH2xe2x80x94, 1-imidazolyl-CH2CH2xe2x80x94, oxazolyl-CH2CH2xe2x80x94, isoxazolyl-CH2CH2xe2x80x94, 3,5-dimethylisoxazol-4-yl-CH2CH2xe2x80x94, phenyl-propyl-;
benzyl-CH(NH2)xe2x80x94, benzyl-CH(NHC(xe2x95x90O)xe2x80x94O-tBu)-, benzyloxy-CH2xe2x80x94, pyrrolidin-2-yl-, or 3-t-butoxycarbonylpyrrolidin-2-yl-;
R5 is xe2x80x94CH3, xe2x80x94CH2CH3, xe2x80x94CH2CH2CH3, xe2x80x94CH(CH3)2, xe2x80x94CH2CH2CH2CH3, xe2x80x94CH(CH3)CH2CH3, xe2x80x94CH2CH(CH3)2, xe2x80x94CH2C(CH3)3, xe2x80x94CH2CH2CH2CH2CH3, xe2x80x94CH(CH3)CH2CH2CH3, xe2x80x94CH2CH(CH3)CH2CH3, xe2x80x94CH2CH2CH(CH3)2, xe2x80x94CH(CH2CH3)2,
xe2x80x94CF3, xe2x80x94CH2CF3, xe2x80x94CH2CH2CF3, xe2x80x94CH2CH2CH2CF3, xe2x80x94CH2CH2CH2CH2CF3,
xe2x80x94CHxe2x95x90CH2, xe2x80x94CH2CHxe2x95x90CH2, xe2x80x94CH2CH2CHxe2x95x90CH2, xe2x80x94CHxe2x95x90CHCH3, cis-CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CH(C6H5), xe2x80x94CH2CHxe2x95x90C(CH3)2, cis-CH2CHxe2x95x90CHCH2CH3, trans-CH2CHxe2x95x90CHCH2CH3, cis-CH2CH2CHxe2x95x90CH(CH3), trans-CH2CH2CHxe2x95x90CH(CH3), trans-CH2CHxe2x95x90CHCH2(C6H5),
xe2x80x94Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1CH, xe2x80x94CH2Cxe2x89xa1C(CH3), xe2x80x94CH2Cxe2x89xa1C(C6H5), xe2x80x94CH2CH2Cxe2x89xa1CH, xe2x80x94CH2CH2Cxe2x89xa1C(CH3), xe2x80x94CH2CH2Cxe2x89xa1C(C6H5), xe2x80x94CH2CH2CH2Cxe2x89xa1CH, xe2x80x94CH2CH2CH2Cxe2x89xa1C(CH3), xe2x80x94CH2CH2CH2Cxe2x89xa1C(C6H5),
cyclopropyl-CH2xe2x80x94, cyclobutyl-CH2xe2x80x94, cyclopentyl-CH2xe2x80x94, cyclohexyl-CH2xe2x80x94, (2-CH3-cyclopropyl)CH2xe2x80x94, (3-CH3-cyclobutyl)CH2xe2x80x94, cyclopropyl-CH2CH2xe2x80x94, cyclobutyl-CH2CH2xe2x80x94, cyclopentyl-CH2CH2xe2x80x94, cyclohexyl-CH2CH2xe2x80x94, (2-CH3-cyclopropyl)CH2CH2xe2x80x94, (3-CH3-cyclobutyl)CH2CH2xe2x80x94,
phenyl-CH2xe2x80x94, (2-F-phenyl)CH2xe2x80x94, (3-F-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2xe2x80x94, (3,5-diF-phenyl)CH2xe2x80x94, 2-furanyl-CH2xe2x80x94, 3-furanyl-CH2xe2x80x94, 2-thienyl-CH2xe2x80x94, 3-thienyl-CH2xe2x80x94, 2-pyridyl-CH2xe2x80x94, 3-pyridyl-CH2xe2x80x94, 4-pyridyl-CH2xe2x80x94, 1-imidazolyl-CH2xe2x80x94, 2-oxazolyl-CH2xe2x80x94, 4-oxazolyl-CH2xe2x80x94, 5-oxazolyl-CH2xe2x80x94, 3-isoxazolyl-CH2xe2x80x94, 4-isoxazolyl-CH2xe2x80x94, 5-isoxazolyl-CH2xe2x80x94,
phenyl-CH2CH2xe2x80x94, (2-F-phenyl)CH2CH2xe2x80x94, (3-F-phenyl)CH2CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, furanyl-CH2CH2xe2x80x94, thienyl-CH2CH2xe2x80x94, pyridyl-CH2CH2xe2x80x94, 1-imidazolyl-CH2CH2xe2x80x94, oxazolyl-CH2CH2xe2x80x94, isoxazolyl-CH2CH2xe2x80x94;
methoxy, ethoxy, propoxy, or butoxy;
R5a is H;
alternatively, R5 and R5a may be combined to form cyclopentyl, cyclohexyl, or cycloheptyl;
W is a bond, xe2x80x94CH2xe2x80x94, or xe2x80x94CH(CH3)xe2x80x94;
X is a bond; 
Y is a bond, xe2x80x94CH2xe2x80x94Vxe2x80x94, xe2x80x94Vxe2x80x94, or xe2x80x94Vxe2x80x94CH2xe2x80x94;
V is a bond, xe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)xe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94NHxe2x80x94, or xe2x80x94N(CH3)xe2x80x94;
Z is H, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF3O-phenyl, 3-CF3O-phenyl, 4-CF3O-phenyl,
furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl, morpholino, N-piperinyl,
phenyl-CH2xe2x80x94, (2-F-phenyl)CH2xe2x80x94, (3-F-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2xe2x80x94, (2-Cl-phenyl)CH2xe2x80x94, (3-Cl-phenyl)CH2xe2x80x94, (4-Cl-phenyl)CH2xe2x80x94, (2,3-diF-phenyl)CH2xe2x80x94, (2,4-diF-phenyl)CH2xe2x80x94, (2,5-diF-phenyl)CH2xe2x80x94, (2,6-diF-phenyl)CH2xe2x80x94, (3,4-diF-phenyl)CH2xe2x80x94, (3,5-diF-phenyl)CH2xe2x80x94, (2,3-diCl-phenyl)CH2xe2x80x94, (2,4-diCl-phenyl)CH2xe2x80x94, (2,5-diCl-phenyl)CH2xe2x80x94, (2,6-diCl-phenyl)CH2xe2x80x94, (3,4-diCl-phenyl)CH2xe2x80x94, (3,5-diCl-phenyl)CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2xe2x80x94, (3-Cl-4-F-phenyl)CH2xe2x80x94, (2-MeO-phenyl)CH2xe2x80x94, (3-MeO-phenyl)CH2xe2x80x94, (4-MeO-phenyl)CH2xe2x80x94, (2-PhO-phenyl)CH2xe2x80x94, (3-PhO-phenyl)CH2xe2x80x94, (4-PhO-phenyl)CH2xe2x80x94, (2-Me-phenyl)CH2xe2x80x94, (3-Me-phenyl)CH2xe2x80x94, (4-Me-phenyl)CH2xe2x80x94, (2-MeS-phenyl)CH2xe2x80x94, (3-MeS-phenyl)CH2xe2x80x94, 4-MeS-phenyl)CH2xe2x80x94, (2-CF3O-phenyl)CH2xe2x80x94, (3-CF3O-phenyl)CH2xe2x80x94, (4-CF3O-phenyl)CH2xe2x80x94, (furanyl)CH2xe2x80x94, (thienyl)CH2xe2x80x94, (pyridyl)CH2xe2x80x94, (2-Me-pyridyl)CH2xe2x80x94, (3-Me-pyridyl)CH2xe2x80x94, (4-Me-pyridyl)CH2xe2x80x94, (1-imidazolyl)CH2xe2x80x94, (oxazolyl)CH2xe2x80x94, (isoxazolyl)CH2xe2x80x94, (1-benzimidazolyl)CH2xe2x80x94, (cyclopropyl)CH2xe2x80x94, (cyclobutyl)CH2xe2x80x94, (cyclopentyl)CH2xe2x80x94, (cyclohexyl)CH2xe2x80x94, (morpholino)CH2xe2x80x94, (N-pipridinyl)CH2xe2x80x94,
phenyl-CH2CH2xe2x80x94, (phenyl)2CHCH2xe2x80x94, (2-F-phenyl)CH2CH2xe2x80x94, (3-F-phenyl)CH2CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, (2-Cl-phenyl)CH2CH2xe2x80x94, (3-Cl-phenyl)CH2CH2xe2x80x94, (4-Cl-phenyl)CH2CH2xe2x80x94, (2,3-diF-phenyl)CH2CH2xe2x80x94, (2,4-diF-phenyl)CH2CH2xe2x80x94, (2,5-diF-phenyl)CH2CH2xe2x80x94, (2,6-diF-phenyl)CH2CH2xe2x80x94, (3,4-diF-phenyl)CH2CH2xe2x80x94, (3,5-diF-phenyl)CH2CH2xe2x80x94, (2,3-diCl-phenyl)CH2CH2xe2x80x94, (2,4-diCl-phenyl)CH2CH2xe2x80x94, (2,5-diCl-phenyl)CH2CH2xe2x80x94, (2,6-diCl-phenyl)CH2CH2xe2x80x94, (3,4-diCl-phenyl)CH2CH2xe2x80x94, (3,5-diCl-phenyl)CH2CH2xe2x80x94, (3-F-4-Cl-phenyl)CH2CH2xe2x80x94, (3-F-5-Cl-phenyl)CH2CH2xe2x80x94, (3-Cl-4-F-phenyl)CH2CH2xe2x80x94, (2-MeO-phenyl)CH2CH2xe2x80x94, (3-MeO-phenyl)CH2CH2xe2x80x94, (4-MeO-phenyl)CH2CH2xe2x80x94, (2-Me-phenyl)CH2CH2xe2x80x94, (3-Me-phenyl)CH2CH2xe2x80x94, (4-Me-phenyl)CH2CH2xe2x80x94, (2-MeS-phenyl)CH2CH2xe2x80x94, (3-MeS-phenyl)CH2CH2xe2x80x94, (4-MeS-phenyl)CH2CH2xe2x80x94, (2-CF3O-phenyl)CH2CH2xe2x80x94, (3-CF3O-phenyl)CH2CH2xe2x80x94, (4-CF3O-phenyl)CH2CH2xe2x80x94, (furanyl)CH2CH2xe2x80x94, (thienyl)CH2CH2xe2x80x94, (pyridyl)CH2CH2xe2x80x94, (2-Me-pyridyl)CH2CH2xe2x80x94, (3-Me-pyridyl)CH2CH2xe2x80x94, (4-Me-pyridyl)CH2CH2xe2x80x94, (imidazolyl)CH2CH2xe2x80x94, (oxazolyl)CH2CH2xe2x80x94, (isoxazolyl)CH2CH2xe2x80x94, (benzimidazolyl)CH2CH2xe2x80x94, (cyclopropyl)CH2CH2xe2x80x94, (cyclobutyl)CH2CH2xe2x80x94, (cyclopentyl)CH2CH2xe2x80x94, (cyclohexyl)CH2CH2xe2x80x94, (morpholino)CH2CH2xe2x80x94, or (N-pipridinyl)CH2CH2xe2x80x94;
R11, at each occurrence, is independently selected from H, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, 2-F-phenyl-, 3-F-phenyl, 4-F-phenyl, 4-Cl-phenyl, 4-CH3-phenyl, 4-MeO-phenyl-, 4-CF3-phenyl, (4-F-phenyl)CH2xe2x80x94, (4-Cl-phenyl)CH2xe2x80x94, (4-CH3-phenyl)CH2xe2x80x94, (4-CF3-phenyl)CH2xe2x80x94, (4-F-phenyl)CH2CH2xe2x80x94, (4-Cl-phenyl)CH2CH2xe2x80x94, (4-CH3-phenyl)CH2CH2xe2x80x94, (4-CF3-phenyl)CH2CH2xe2x80x94, pyridin-2-yl-, pyridin-3-yl-, 4-CF3-pyridin-2-yl-, 4-CH3-pyridin-2-yl-, thiazol-2-yl-, azapan-1-yl, N,N-dimethylamino, N,N-diethylamino, N,N-dipropylamino, and N,N-dibutylamino; and
R13, at each occurrence, is independently selected from H, MeO, F, and Cl.
[18] In a preferred embodiment the present invention provides a compound of Formula (If); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[19] In a preferred embodiment the present invention provides a compound of Formula (Ig); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[20] In a preferred embodiment the present invention provides a compound of Formula (Ih); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[21] In a preferred embodiment the present invention provides a compound of Formula (Ii); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[22] In a preferred embodiment the present invention provides a compound of Formula (Ij); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[23] In a preferred embodiment the present invention provides a compound of Formula (Ik); 
or a pharmaceutically acceptable salt form or prodrug thereof.
[24] In a preferred embodiment the present invention provides a compound selected from:
(2R,3S)-N-[1-butyl-5-(methylethyl)-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)]-2-(cyclopropylmethyl)-3-hydroxyheptanamide;
(2R,3S)-2-(cyclopropylmethyl)-3-hydroxy-N-[5-(methylethyl)-2-oxo-1-benzyl(3H-benzo[f]1,4-diazepin-3-yl)]heptanamide;
(2R,3S)-2-(cyclopropylmethyl)-3-hydroxy-N-{5-methyl-1-[(3-{[(4-methylphenyl)sulfonyl]amino}phenyl)methyl]-2-oxo(3H-benzo[f]1,4-diazepin-3-yl)}heptanamide; 3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-t-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
(2R,3S)-2-(cyclopropylmethyl)-3-hydroxy-N-{1-[(3-{[(4-methylphenyl)sulfonyl]amino}phenyl)methyl]-2-oxo(3H,4H,5H-benzo[f]1,4-diazaperhydroepin-3-yl)}heptanamide;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-piperizinyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
7-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(2-diethylaminoethyl)-6,7-dihydro-5H-dibenzoazepin-6-one;
7-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-(3-hydroxypropyl)-6,7-dihydro-5H-dibenzoazepin-6-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(benzyl-5-(2,2-dimethylpropyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-n-butyl-5-n-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-benzyl-5-n-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(3,4-dihydro-1H-isoquinolin-2-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(2,2-dimethylpropyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
7-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-n-butyl-6,7-dihydro-5H-dibenzoazepin-6-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(2-ethylbutyl)-5-n-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-pyrrolidin-1-yl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
7-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-5-benzyl-6,7-dihydro-5H-dibenzoazepin-6-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(3-hydroxypropyl)-5-t-butyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-ethoxy-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-butyl-5-(2,2-dimethylpropyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(2-pyridinylmethyl N-oxide)-5-(4-trifluoromethyl)phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(3-pyridinylmethyl N-oxide)-5-(4-trifluoromethyl)phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(S)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxopentyl)amino-1-(3-pyridynylmethyl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(2-(diethylamino)ethyl)-5-(4-trifluoromethylphenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxopentyl)amino-1-(3-pyridinylmethyl N-oxide)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
(2R,3S)-N-(8-bromo-1,5-dimethyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)-2-(cyclopropylmethyl)-3-hydroxyheptanamide;
6-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1,4-dibenzyl-hexahydro-5H-1,4-diazepin-5-one;
6-(2-(R)-cyclopropylmethyl-3-(S)-hydroxy-1-oxohetptyl)amino-4-benzyl-1-[(4-chlorophenyl)sulfonyl]-hexahydro-5H-1,4-diazepin-5-one;
6-(2-(R)-cyclopropylmethyl-3-(S)-hydroxy-1-oxopentyl)amino-4-benzyl-1-[(4-chlorophenyl)sulfonyl]-hexahydro-5H-1,4-diazepin-5-one;
(2R,3S)-2-(cyclopropylmethyl)-N-(1-{[3-(4-fluorophenoxy)phenyl]methyl}-2-oxo(3H,4H,5H-benzo[f]azaperhydroepin-3-yl))-3-hydroxyheptanamide;
(2R,3S)-2-(cyclopropylmethyl)-3-hydroxy-N-[2-oxo-1-benzyl(3H,4H,5H-benzo[f]azaperhydroepin-3-yl)]heptanamide;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-benzylpiperizin-1-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-methanesulfonyl-piperazin-1-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-acetylpiperazin-1-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-([4-(3,5-dimethyl-isoxazole-4-sulfonyl)-piperazin-1-yl]-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
3-(R,S)-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-methyl-5-(4-benzoylpiperazin-1-yl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one;
4-[3-(2-(R)-Cyclopropylmethyl-3-(S)-hydroxyheptanoylamino)-1-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl]-piperazine-1-carboxylic acid tert-butyl ester; and
3-(2-(R)-cyclopropylmethyl-3-(S)-hydroxyl-1-oxoheptyl)amino-1-(3-pyridinylmethyl N-oxide)-5-(4-trifluoromethyl)phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one-4-N-oxide.
In another preferred embodiment the present invention provides all herein disclosed embodiments with the proviso that when R5 and R5a are not simultaneaously H.
In another preferred embodiment the present invention provides all herein disclosed embodiments with the proviso that when Q is a 9 membered benzofused heterocyclic group substituted by 0, 1, or 2 R1a, then R3 is H.
In another preferred embodiment the present invention provides all herein disclosed embodiments with the proviso that when xe2x80x94WXYZ is a tertiary butyl group and R5 is either C1-C4 alkyl or C2 alkenyl, then Q is not phenyl substituted by 0, 1 or 2 R1a.
In another preferred embodiment the present invention provides all herein disclosed embodiments with the proviso that when R5 is C1-C3 alkyl, then Q is not phenyl substituted by 0, 1 or 2 R1a.
In another preferred embodiment the present invention provides all herein disclosed embodiments with the proviso that the moiety: 
of Formula (I), et seq., is not a C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C10 cycloalkyl-C1-C4 alkyl, C3-C10 cycloalkyl, C1-C4 alkyl-Oxe2x80x94C1-C4 alkyl, C1-C4 alkyl-Sxe2x80x94C1-C4 alkyl, C2-C4 alkyl-NR20xe2x80x94C2-C4 alkyl, C2-C4 alkyl-C6-C10 aryl, C2-C4 alkyl-C6-C10 cycloalkyl, C2-C8 alkenyl, C6-C10 aryl-C1-C4 alkyl, C6-C10 aryl-C2-C4-alkynyl, indol-3-yl-C1-C3 alkyl, and imidazol-4-yl-C1-C3 alkyl; where the alkyl group is substituted with OH.
In another preferred embodiment the present invention provides all herein disclosed embodiments with the proviso that the moiety: 
of Formula (I), et seq., is not a C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C10 cycloalkyl-C1-C4 alkyl, C3-C10 cycloalkyl, C1-C4 alkyl-Oxe2x80x94C1-C4 alkyl, C1-C4 alkyl-Sxe2x80x94C1-C4 alkyl, C2-C4 alkyl-NR20xe2x80x94C2-C4 alkyl, C2-C4 alkyl-C6-C10 aryl, C2-C4 alkyl-C6-C10 cycloalkyl, C2-C8 alkenyl, C6-C10 aryl-C1-C4 alkyl, C6-C10 aryl-C2-C4-alkynyl, indol-3-yl-C1-C3 alkyl, and imidazol-4-yl-C1-C3 alkyl; where the alkyl group is substituted with OH.
In a second embodiment, the present invention provides a pharmaceutical composition comprising a compound of Formula (I) and a pharmaceutically acceptable carrier.
In a third embodiment, the present invention provides a method for the treatment of a neurological disorder associated with xcex2-amyloid production comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of Formula (I).
In a preferred embodiment the neurological disorder associated with xcex2-amyloid production is Alzheimer""s Disease.
In a fourth embodiment, the present invention provides a method for inhibiting xcex3-secretase activity for the treatment of a physiological disorder associated with inhibiting xcex3-secretase activity comprising administering to a host in need of such inhibition a therapeutically effective amount of a compound of Formula (I) that inhibits xcex3-secretase activity.
In a preferred embodiment the physiological disorder associated with inhibiting xcex3-secretase activity is Alzheimer""s Disease.
In a fifth embodiment, the present invention provides a compound of Formula (I) for use in therapy.
In a preferred embodiment the present invention provides a compound of Formula (I) for use in therapy of Alzheimer""s Disease.
In a sixth embodiment, the present invention provides for the use of a compound of Formula (I) for the manufacture of a medicament for the treatment of Alzheimer""s Disease.
As used herein, the term xe2x80x9cAxcex2xe2x80x9d denotes the protein designated Axcex2, xcex2-amyloid peptide, and sometimes xcex2/A4, in the art. Axcex2 is an approximately 4.2 kilodalton (kD) protein of about 39 to 43 amino acids found in amyloid plaques, the walls of meningeal and parenchymal arterioles, small arteries, capillaries, and sometimes, venules. The isolation and sequence data for the first 28 amino acids are described in U.S. Pat. No. 4,666,829. The 43 amino acid sequence is:
The term xe2x80x9cAPPxe2x80x9d, as used herein, refers to the protein known in the art as xcex2 amyloid precursor protein. This protein is the precursor for Axcex2 and through the activity of xe2x80x9csecretasexe2x80x9d enzymes, as used herein, it is processed into Axcex2. Differing secretase enzymes, known in the art, have been designated xcex2 secretase, generating the N-terminus of Axcex2, (secretase cleaving around the 16/17 peptide bond in Axcex2, and xe2x80x9cxcex3 secretasesxe2x80x9d, as used herein, generating C-terminal Axcex2 fragments ending at position 38, 39, 40, 42, and 43 or generating C-terminal extended precursors which are subsequently truncated to the above polypeptides
The compounds herein described may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins, Cxe2x95x90N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated.
The term xe2x80x9csubstituted,xe2x80x9d as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom""s normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., xe2x95x90O), then 2 hydrogens on the atom are replaced.
When any variable (e.g., R1a, R4a, R13 etc.) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-3 R1a, then said group may optionally be substituted with up to three R1a groups and R1a at each occurrence is selected independently from the definition of R1a. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.
When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.
As used herein, xe2x80x9calkylxe2x80x9d or xe2x80x9calkylenexe2x80x9d is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms; for example, xe2x80x9cC1-C6 alkylxe2x80x9d denotes alkyl having 1 to 6 carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, pentyl, and hexyl. Preferred xe2x80x9calkylxe2x80x9d group is xe2x80x9cC1-C4 alkylxe2x80x9d wherein methyl, ethyl, n-propyl, i-propyl, n-butyl, and i-butyl, are specifically preferred. As used herein, xe2x80x9cC1-C3 alkylxe2x80x9d, whether a terminal substituent or a alkylene group linking two substituents, is understood to specifically include both branched and straight-chain methyl, ethyl, and propyl.
As used herein, xe2x80x9calkenylxe2x80x9d or xe2x80x9calkenylenexe2x80x9d is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbonxe2x80x94carbon bonds which may occur in any stable point along the chain. Examples of xe2x80x9cC2-C6 alkenylxe2x80x9d include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 2-pentenyl, 3-pentenyl, hexenyl, and the like.
As used herein, xe2x80x9calkynylxe2x80x9d or xe2x80x9calkynylenexe2x80x9d is intended to include hydrocarbon chains of either a straight or branched configuration and one or more carbonxe2x80x94carbon triple bonds which may occur in any stable point along the chain, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, and the like.
xe2x80x9cAlkoxyxe2x80x9d or xe2x80x9calkyloxyxe2x80x9d represents an alkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy. Similarly, xe2x80x9calkylthioxe2x80x9d or xe2x80x9cthioalkoxyxe2x80x9d is represents an alkyl group as defined above with the indicated number of carbon atoms attached through a sulphur bridge.
xe2x80x9cHaloxe2x80x9d or xe2x80x9chalogenxe2x80x9d as used herein refers to fluoro, chloro, bromo, and iodo. Unless otherwise specified, preferred halo is fluoro and chloro. xe2x80x9cCounterionxe2x80x9d is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, sulfate, and the like.
xe2x80x9cHaloalkylxe2x80x9d is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogen (for example xe2x80x94CvFw where v=1 to 3 and w=1 to (2v+1)). Examples of haloalkyl include, but are not limited to, trifluoromethyl, trichloromethyl, pentafluoroethyl, pentachloroethyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl, heptafluoropropyl, and heptachloropropyl. xe2x80x9cHaloalkoxyxe2x80x9d is intended to mean a haloalkyl group as defined above with the indicated number of carbon atoms attached through an oxygen bridge; for example trifluoromethoxy, pentafluoroethoxy, 2,2,2-trifluoroethoxy, and the like. xe2x80x9cHalothioalkoxyxe2x80x9d is intended to mean a haloalkyl group as defined above with the indicated number of carbon atoms attached through a sulphur bridge.
xe2x80x9cCycloalkylxe2x80x9d is intended to include saturated ring groups, having the specified number of carbon atoms. For example, xe2x80x9cC3-C6 cycloalkylxe2x80x9d denotes such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.
As used herein, xe2x80x9ccarbocyclexe2x80x9d is intended to mean any stable 3- to 7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic or tricyclic, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin). Preferred example of xe2x80x9cC3-C10 carbocyclexe2x80x9d or xe2x80x9cC3-C6 carbocyclexe2x80x9d is C3-C6 cycloalkyl, specifically cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
As used herein, the term xe2x80x9cheterocyclexe2x80x9d or xe2x80x9cheterocyclic ringxe2x80x9d is intended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7- to 14-membered bicyclic heterocyclic ring which is saturated partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and 1, 2, 3 or 4 heteroatoms, preferably 1, 2, or 3 heteroatoms, independently selected from the group consisting of N, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. If specifically noted, a nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1.
Examples of heterocycles include, but are not limited to, 1H-indazole, 2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl, 4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazolyl, 4aH-carbazolyl, b-carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, homopiperidinyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinylperimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, N-oxide-pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, xanthenyl. Preferred 5 to 10 membered heterocycles include, but are not limited to, pyridinyl, N-oxide-pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, tetrazolyl, benzofuranyl, benzothiofuranyl, indolyl, benzimidazolyl, 1H-indazolyl, oxazolidinyl, isoxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, quinolinyl, and isoquinolinyl. Preferred 5 to 7 membered heterocycles include, but are not limited to, pyridinyl, N-oxide-pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, tetrazolyl; more preferred 5 to 7 membered heterocycles include, but are not limited to, pyridinyl, N-oxide-pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, piperazinyl, piperidinyl, homopiperidinyl, pyrazolyl, imidazolyl, and tetrazolyl. Preferred 5 to 6 membered heterocycles include, but are not limited to, pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, tetrazolyl; more preferred 5 to 6 membered heterocycles include, but are not limited to, pyridinyl, N-oxide-pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, and tetrazolyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.
As used herein, the term xe2x80x9carylxe2x80x9d, xe2x80x9cC6-C10 arylxe2x80x9d or aromatic residue, is intended to mean an aromatic moiety containing the specified number of carbon atoms; for example phenyl, pyridinyl or naphthyl. Unless otherwise specified, xe2x80x9carylxe2x80x9d may be unsubstituted or substituted with 0 to 3 groups selected from H, OH, OCH3, Cl, F, Br, I, CN, NO2, NH2, N(CH3)H, N(CH3)2, CF3, OCF3, C(xe2x95x90O)CH3, SCH3, S(xe2x95x90O)CH3, S(xe2x95x90O)2CH3, CH3, CH2CH3, CO2H, and CO2CH3.
The phrase xe2x80x9cadditional lactam carbonsxe2x80x9d, as used herein, is intended to denote the number of optional carbon atoms in the lactam ring B of Formula (I). Formula (I*): 
represents the lactam ring B of Formula (I). Additional lactam carbons are carbons in lactam ring B other than the carbons numbered 2 and 3 in the backbone of the formula. The additional lactam carbons may be optionally replaced by a heteroatom selected from oxygen, nitrogen and sulfur. Lactam ring B contains 1, 2, 3, 4, 5, 6 or 7 optional carbons, wherein one optional carbon may optionally be replaced by a heteroatom, such that the total number of members of lactam ring B, including atoms numbered 1, 2 and 3 in the backbone, does not exceed 10. It is preferred that the total number of atoms of lactam ring B is 6, 7 or 8; it is more preferred that the total number of atoms of lactam ring B is seven. Examples of lactam ring B include: 
but are not intended to limit the invention. Preferred examples of lactam ring B are B1, B2, B5, B6, B8, B9, B13, and B16; more preferred examples of lactam ring B are B1, B6, B8, B9, and B13. Preferred examples of substituent R10 or R11 on lactam B are methyl, ethyl, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl, and (4-trifluorophenyl)methyl. Preferred examples of substituent R13 on fused rings of lactam B are methyl, fluoro, and chloro.
The compounds herein described may have asymmetric centers. One enantiomer of a compound of Formula (I) may display superior biological activity over the opposite enantiomer. For example carbon 3 of lactam ring B Formula (Ixe2x80x3) may exist in either an S or R configuration. Thus, an R or S configuration at carbon 3 in Formula (Ixe2x80x3) is considered part of the invention. An example of such configuration includes, 
but is not intended to be limited to this example of ring B. When required, separation of the racemic material can be achieved by methods known in the art. Additionally, the carbon atoms to which the OH and R5 are attached may describe chiral carbons which may display superior biological activity over the opposite enantiomer. For example, where Q and R5 are not H, then the configuration of the two centers may be described as (2R,3R), (2R,3S), (2S,3R), or (2S,3S). All configurations are considered part of the invention; however, the (2R,3S) and the (2S,3R) are preferred and the (2R,3S) is more preferred.
The phrase xe2x80x9cpharmaceutically acceptablexe2x80x9d is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
As used herein, xe2x80x9cpharmaceutically acceptable saltsxe2x80x9d refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.
The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington""s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference.
xe2x80x9cProdrugsxe2x80x9d are intended to include any covalently bonded carriers which release the active parent drug according to formula (I) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of formula (I) are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of formula (I) wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug or compound of formula (I) is administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formula (I), and the like.
xe2x80x9cStable compoundxe2x80x9d and xe2x80x9cstable structurexe2x80x9d are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.
The compounds of the present invention can be prepared in a number of ways well known to one skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those described below. All references cited herein are hereby incorporated in their entirety by reference.
The novel compounds of this invention may be prepared using the reactions and techniques described in this section. The reactions are performed in solvents appropriate to the reagents and materials employed and are suitable for the transformations being effected. Also, in the description of the synthetic methods described below, it is to be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and workup procedures, are chosen to be the conditions standard for that reaction, which should be readily recognized by one skilled in the art. It is understood by one skilled in the art of organic synthesis that the functionality present on various portions of the molecule must be compatible with the reagents and reactions proposed. Such restrictions to the substituents which are compatible with the reaction conditions will be readily apparent to one skilled in the art and alternate methods must then be used. 
Aldol derivatives can be prepared by the procedure of Evans (D. A. Evans et al, Org. Synth. 1990, 68, 83-90), which is outlined in Scheme 1 where acylation of an oxazolidinone with an acid chloride provides structure 2. Asymmetric aldol reaction to form 3 followed by cleavage of the chiral auxiliary yielding xcex2-hydroxycarboxylic acid 4. Additional examples are found in D. A. Evans Aldrichimica Acta 1982, 15, 23-32. Alternative syntheses of structures 4 can be accomplished by the methods of Crimmins (M. T. Crimmins et al, J. Am. Chem. Soc. 1997, 119, 7883-7884), Paterson (I. Paterson et al, Org. React. 1997, 51, 1-200) and Mukaiyama (T. Mukaiyama et al, Org. React. 1994, 1-104). Anti-aldols may be synthesized according to: (a) A. K. Ghosh, J. Am. Chem. Soc. 1996, 118, 2527-2528, or (b) S. Masamune et al., J. Am. Chem. Soc. 1997, 119, 2586. 
Carboxylic acids of formula 4 can be coupled to an appropriate lactam intermediate using methods commonly used in peptide syntheses, such as DCC, EDC, CDI, BOP, PyBOP, HATU, HBTU and phenyl ester mediated coupling, as described in A. R. Chamberlin, Chem. Rev. 1997, 97, 2243-2266. Compound 6 is synthesized, as illustrated in Scheme 2, by coupling acid 4 with 3-amino-1,4-benzodiazepin-2-one 5 under the catalysis of EDC and HOBt providing the final compound 6 (S. Nozaki et al, Bull. Chem. Soc. Jpn. 1982, 55, 2165-2168).
Similarly, Schemes 2a and 2b illustrate synthesis of bisbenzodiazepine and lactam compounds of the present invention: 
Methods for the synthesis of lactam intermediates as contemplated by the present invention useful in the synthesis of compounds of Formula (I), including amino benzodiazepinones, dibenzo azepinones and other related heterocycles, are known in the art and are disclosed in a number of references including PCT publication number WO 98/28268, WO 99/66934, WO 00/07995, and WO 00/38618, which are hereby incorporated by reference. Additional references include Bock, et al, J. Org. Chem., 1987, 52, 3232-3239; Sherrill et al, J. Org. Chem., 1995, 60, 730-734; and Walsh, D. A., Synthesis, September 1980, p.677; and Brown, et al., Tetrahedron Letters, 1971, 8, 667-670.
Synthetic approaches to aminobenzodiazepines are widely described in the literature and well known to one skilled in the art. The typical methods are illustrated, but are not limited to, the following references. See (a) M. G. Bock et al., J. Org. Chem., 1987, 52, 3232; (b) R. G. Sherrill et al., J. Org. Chem., 1995, 60, 734; (c) M. G. Bock et al., J. Med. Chem., 1989, 32, 13-16; (d) J. L. Castro et al., J. Med. Chem., 1997, 40, 2491-2501; (e) M. S. Chambers et al., Bioorg. and Med. Chem. Lett., 1993, 3 (10), 1919-1924; (f) J. H. Gogerty et al., J. Med. Chem., 1977, 20 (7), 952; (g) G. Semple et al., Bioorg. and Med. Chem. Lett., 1996, 6(1), 51-54; (h) G. Semple et al., J. Med. Chem., 1997, 40, 331-341; (i) G. Semple et al., Bioorg. and Med. Chem. Lett., 1996, 6 (1), 55-58; (j) G. Semple et al., Synth. Commun., 1996, 26 (4), 721-727; and (k) G. A. Showell et al., J. Med. Chem., 1994, 37, 719-721. For general synthetic descriptions of 2-aminobenzophenone with various substitutions used in the preparation of benzodiazepines, see D. A. Walsh, Synthesis 1980, 677. 
The preparation of aldehyde Qxe2x80x94CHO with general structure of 9 is shown in Scheme 3 (H. C. Arndt, Synthesis 1979, 202-204). Allyl ether 8 can be made from the action of an alkoxide generated in DMF with allyl bromide, which is converted to xcex1-alkoxy- or aryloxyaldehyde 9 using a two-phase osmium tetraoxide oxidation. 
As shown in Scheme 4, aldehyde Qxe2x80x94CHO of general structure 12 can be prepared in the same fashion from the corresponding allyl benzyl ether, which is readily available according to the procedure described by P. Kocienski (P. Kocienski Tetrahedron 1990, 46, 1767-1782).
The aldehydes used in Scheme 1 are either commercially available, prepared from commercially available or readily accessible alcohols, or prepared from commercially available or readily accessible carboxylic acids. For preparation of other non-commercially available aldehydes from commercially available or readily accessible alcohols by oxidation of the corresponding alcohols, see(a) S. V. Ley et al Synthesis 1994, 639; (b) D. Swern, Synthesis 1981, 165-185; and (c) R. C. Larock, Comprehensive Organic Transformations, Wiley-VCH: 1989; pp604-614. For preparation of other non-commercially available aldehydes from commercially available or readily accessible carboxylic acids by reducing the corresponding Weinreb amides or reduction of carboxylic acid derivatives, see (a) S. M. Weinreb et al. Tetrahedron Lett. 1981, 22, 3815-3818; (b) M. Braun, Synthesis 1989, 856; and (c) D. A. Evans, J. Org. Chem. 1993, 58, 2446-2453.
Aminoaldehydes used in the synthesis of the compounds of the invention may be prepared by oxidation of corresponding amino alcohols or reduction of corresponding amino acids; see(a) J. Jurczak et al., Synlett 1993, 241; and (b) S. G. Davis et al., Synlett 1995, 700.
Sulfur containing aldehydes used in the synthesis of compounds of the invention may be made by conjugate addition of a thiol to xcex1,xcex2-unsaturated aldehydes or reaction of a thiol with a halosubstituted aldehyde. See T. Cohen et al., J. Org. Chem. 1995, 60, 2022; Tetrahdron 1994, 50, 12793-12810; J. Org. Chem. 1992, 57, 6; Phosphorus, Sulfur, and Silicon 1993, 74, 1; and Tetrahdron 1994, 50, 11569-11584.
Sulfoxides and sulfones are prepared from the corresponding sulfide by oxidation. See M. Hudlicky, Oxidations in Organic Chemistry, ACS, 1990; pp 250-264.
The acid chlorides used in Scheme 1 are either commercially available or prepared from commercially available or readily accessible carboxylic acids by the action of oxalyl chloride or thionyl chloride. See R. C. Larock, Comprehensive Organic Transformations, Wiley-VCH: 1989; pp963-964.